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Sample records for chagosensis leucettidae founder

  1. The founder's dilemma.

    PubMed

    Wasserman, Noam

    2008-02-01

    Why do people start businesses? For the money and the chance to control their own companies, certainly. But new research from Harvard Business School professor Wasserman shows that those goals are largely incompatible. The author's studies indicate that a founder who gives up more equity to attract cofounders, new hires, and investors builds a more valuable company than one who parts with less equity. More often than not, however, those superior returns come from replacing the founder with a professional CEO more experienced with the needs of a growing company. This fundamental tension requires founders to make "rich" versus "king" trade-offs to maximize either their wealth or their control over the company. Founders seeking to remain in control (as John Gabbert of the furniture retailer Room & Board has done) would do well to restrict themselves to businesses where large amounts of capital aren't required and where they already have the skills and contacts they need. They may also want to wait until late in their careers, after they have developed broader management skills, before setting up shop. Entrepreneurs who focus on wealth, such as Jim Triandiflou, who founded Ockham Technologies, can make the leap sooner because they won't mind taking money from investors or depending on executives to manage their ventures. Such founders will often bring in new CEOs themselves and be more likely to work with their boards to develop new, post-succession roles for themselves. Choosing between money and power allows entrepreneurs to come to grips with what success means to them. Founders who want to manage empires will not believe they are successes if they lose control, even if they end up rich. Conversely, founders who understand that their goal is to amass wealth will not view themselves as failures when they step down from the top job.

  2. [Founder mutation in Lynch syndrome].

    PubMed

    Cajal, Andrea R; Piñero, Tamara A; Verzura, Alicia; Santino, Juan Pablo; Solano, Angela R; Kalfayan, Pablo G; Ferro, Alejandra; Vaccaro, Carlos

    2016-01-01

    Lynch syndrome is the most frequent syndrome in hereditary colorectal cancer, a family-specific deleterious mutations in genes encoding DNA reparation proteins: MLH1 (mutL homolog 1), MSH2, MSH6 (mutS homolog 2 y 6, respectively), PMS2 (PMS1 homolog 2, mismatch repair system component) y MUTYH (mutY DNA glycosylase). The c.2252_2253delAA, p.Lys751Serfs*3 mutation in MLH1 gene segregates with a haplotype reported in the northern region of Italy and whose origin was attributed to a founder effect. This mutation co-segregates with typical characteristics of Lynch syndrome, including early age at onset and multiple primary tumors in the same individual, a high frequency of pancreatic cancer, high microsatellite instability and lack of PMS2 expression. This report describes a mutation in an Argentinian patient with endometrioid adenocarcinoma of uterus. Her first-degree relatives had a history of colon cancer diagnosed before 50 years, fulfilling the Amsterdam Criteria I and Lynch syndrome II. The high pathogenicity associated to this mutation makes necessary the study of all members from families with hereditary cancer, allowing pre-symptomatic genetic diagnosis, early assessment and the instauration of preventive treatments.

  3. Manic depressive illness in a founder population.

    PubMed

    Heyer, Evelyne; Toupance, Bruno; Perri, Cesare; De Vito, Ornella; Foncin, Jean-François; Cecilia Bruni, Amalia

    2003-08-01

    Manic depressive illness (MDI) segregates within a founder population originating from S, a mountain village in Southern Italy. Identity by descent of affected persons cannot be established by direct genealogical methods. A 56 000 persons family reconstruction data base encompasses the whole population of S in the 17th and 18th centuries, and part of the population of S and neighbouring villages in the 19th and 20th centuries. We selected 10 MDI probands who were members of the S population and not evident close relatives of each other. A total of 10 other MDI probands not evidently related to the S population formed a first control group. A second control group was formed with 10 not closely related persons originating within the S population. We determined the founders common ancestors to all the probands of one group but not ancestors to the probands of other groups, and computed the genetic contribution of each founder to each proband. The distance between probands in the S MDI group was calculated with respect to all the founders. In all, 17 founders present in the ascendancy of all individuals of the S MDI group are not present in the ascendancy of the control groups: MDI patients are derived from a subpopulation within S. Two S MDI probands are far from one another in respect of the 'nonspecific' founders, but are very close in respect of the specific founders: a putative MDI trait originated from specific founders of the MDI subpopulation, and hence is identical by descent in the S population.

  4. Moving Forward with Founders: Strategies for Change in Volunteer Organizations

    ERIC Educational Resources Information Center

    Huff, Paula Rogers; Pleskac, Sue

    2012-01-01

    Founder's Syndrome can create barriers to change in Extension programs. As a result, Extension staff have experienced challenges in effecting organizational change where Founders are present. 4-H Youth Development staff in Wisconsin applied a variety of strategies to move forward with 4-H programming, despite the influence of the Founders.…

  5. Founder mitochondrial haplotypes in Amerindian populations.

    PubMed Central

    Bailliet, G.; Rothhammer, F.; Carnese, F. R.; Bravi, C. M.; Bianchi, N. O.

    1994-01-01

    It had been proposed that the colonization of the New World took place by three successive migrations from northeastern Asia. The first one gave rise to Amerindians (Paleo-Indians), the second and third ones to Nadene and Aleut-Eskimo, respectively. Variation in mtDNA has been used to infer the demographic structure of the Amerindian ancestors. The study of RFLP all along the mtDNA and the analysis of nucleotide substitutions in the D-loop region of the mitochondrial genome apparently indicate that most or all full-blooded Amerindians cluster in one of four different mitochondrial haplotypes that are considered to represent the founder maternal lineages of Paleo-Indians. We have studied the mtDNA diversity in 109 Amerindians belonging to 3 different tribes, and we have reanalyzed the published data on 482 individuals from 18 other tribes. Our study confirms the existence of four major Amerindian haplotypes. However, we also found evidence supporting the existence of several other potential founder haplotypes or haplotype subsets in addition to the four ancestral lineages reported. Confirmation of a relatively high number of founder haplotypes would indicate that early migration into America was not accompanied by a severe genetic bottleneck. PMID:7517626

  6. BRCA1 founder mutations compared to ovarian cancer in Belarus.

    PubMed

    Savanevich, Alena; Oszurek, Oleg; Lubiński, Jan; Cybulski, Cezary; Dębniak, Tadeusz; Narod, Steven A; Gronwald, Jacek

    2014-09-01

    In Belarus and other Slavic countries, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases, but the data on contribution of these mutations to ovarian cancers are limited. To estimate the proportion of ovarian cancers in Belarus, which are dependent on BRCA1 Slavic founder mutations, we sought the presence of three most frequent mutations (BRCA1: 5382insC, C61G and, 4153delA) in 158 consecutive unselected cases of ovarian cancer. One of the three founder mutations was present in 25 of 158 unselected cases of ovarian cancer (15.8 %). We recommend that all cases of ovarian cancer in Belarus be offered genetic testing for these founder mutations. Furthermore, genetic testing of the Belarusian population will provide the opportunity to prevent a significant proportion of ovarian cancer.

  7. Variation in founder groups promotes establishment success in the wild.

    PubMed

    Forsman, Anders; Wennersten, Lena; Karlsson, Magnus; Caesar, Sofia

    2012-07-22

    Environmental changes currently pose severe threats to biodiversity, and reintroductions and translocations are increasingly used to protect declining populations and species from extinction. Theory predicts that establishment success should be higher for more variable groups of dissimilar individuals. To test this 'diversity promotes establishment' hypothesis, we introduced colour polymorphic pygmy grasshoppers (Tetrix subulata) to different sites in the wild. The number of descendants found at the release sites the subsequent year increased with increasing number of colour morphs in the founder group, and variation in founder groups also positively affected colour morph diversity in the established populations. Since colour morphs differ in morphology, physiology, behaviour, reproductive life history and types of niche used, these findings demonstrate that variation among individuals in functionally important traits promotes establishment success under natural conditions, and further indicate that founder diversity may contribute to evolutionary rescue and increased population persistence.

  8. Beringian Standstill and Spread of Native American Founders

    PubMed Central

    Tamm, Erika; Kivisild, Toomas; Reidla, Maere; Metspalu, Mait; Smith, David Glenn; Mulligan, Connie J.; Bravi, Claudio M.; Rickards, Olga; Martinez-Labarga, Cristina; Khusnutdinova, Elsa K.; Fedorova, Sardana A.; Golubenko, Maria V.; Stepanov, Vadim A.; Gubina, Marina A.; Zhadanov, Sergey I.; Ossipova, Ludmila P.; Damba, Larisa; Voevoda, Mikhail I.; Dipierri, Jose E.; Villems, Richard; Malhi, Ripan S.

    2007-01-01

    Native Americans derive from a small number of Asian founders who likely arrived to the Americas via Beringia. However, additional details about the intial colonization of the Americas remain unclear. To investigate the pioneering phase in the Americas we analyzed a total of 623 complete mtDNAs from the Americas and Asia, including 20 new complete mtDNAs from the Americas and seven from Asia. This sequence data was used to direct high-resolution genotyping from 20 American and 26 Asian populations. Here we describe more genetic diversity within the founder population than was previously reported. The newly resolved phylogenetic structure suggests that ancestors of Native Americans paused when they reached Beringia, during which time New World founder lineages differentiated from their Asian sister-clades. This pause in movement was followed by a swift migration southward that distributed the founder types all the way to South America. The data also suggest more recent bi-directional gene flow between Siberia and the North American Arctic. PMID:17786201

  9. Genetic Studies of Stuttering in a Founder Population

    ERIC Educational Resources Information Center

    Wittke-Thompson, Jacqueline K.; Ambrose, Nicoline; Yairi, Ehud; Roe, Cheryl; Cook, Edwin H.; Ober, Carole; Cox, Nancy J.

    2007-01-01

    Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions…

  10. Utilization of founder lines for improved Citrus biotechnology via RMCE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    On October 1st 2011 the CRB chose to fund a unique research project, the development of citrus cultivars specifically for genetic engineering (GE). The objective of this research was to develop GE citrus ‘Founder Lines’ containing DNA sequences that will allow the precise insertion of genes for de...

  11. Founders' Continuing Roles in Schools Supporting Self-Directed Learning

    ERIC Educational Resources Information Center

    Nash, Carol

    2014-01-01

    What should be the continuing role of founders in schools supporting self-directed learning? To answer this, the founders' views of two North American schools for self-directed learners will be compared. One school is exam-focused and private; the other is, test-free and public. The founders of both schools have comparable beliefs regarding…

  12. 50 years of Dutch immunology--founders, institutions, highlights.

    PubMed

    Gmelig-Meyling, Frits H J; Meyaard, Linde; Mebius, Reina E

    2014-12-01

    At the occasion of the 50th anniversary of the Dutch Society for Immunology (DSI, de Nederlandse Vereniging voor Immunologie), this contribution deals with some highlights of 50 years of Immunology in the Netherlands. It narrates about the founders and first board members of the DSI, their institutes, progeny and patrimony, describes major centers of immunological activities, mentions key persons in the field, and touches upon some events dear to the Society and its members.

  13. Of Founder Populations, Long QT Syndrome, and Destiny

    PubMed Central

    Schwartz, Peter J.; Brink, Paul A.

    2009-01-01

    Founder populations, characterized by a single ancestor affected by LQTS and by a large number of individuals and families all related to the ancestor and thereby carrying the same disease-causing mutation, represent the ideal human model to study the role of “modifier genes” in the long QT syndrome (LQTS). This chapter reviews some of the fundamental concepts related to founder populations and provides the necessary historic background to understand why so many can be found in South Africa. The focus then moves onto a specific LQT1 founder population, carrier of the A341V mutation, that has been extensively studied during the last 10 years and has provided a significant number of previously unforeseen information. These novel findings range from an unusually high clinical severity not explained by the electrophysiological characteristics of the mutation, to the importance of the tonic and reflex control of heart rate for risk stratification, to the identification of the first modifier genes for the clinical severity of LQTS. PMID:19880070

  14. Uplift of the Colorado Plateau via Lower Crustal Foundering

    NASA Astrophysics Data System (ADS)

    Erdman, M.; Lee, C. T.; Jiang, H.

    2014-12-01

    How the Colorado Plateau reached its current elevation with little internal deformation compared to surrounding regions has perplexed researchers for nearly a century. Hypotheses to explain the two kilometers of uplift since the Late Cretaceous range from delamination of the Farallon plate following flat slab subduction, thermal expansion of upwelling mantle, dynamic topography in response to mantle upwelling, mid-crustal flow from over-thickened crust, and foundering of a dense lower crustal root. Many of these hypotheses are constrained by geodynamic modelling with limited evidence from the rock record. We report here the petrologic and geochemical makeup of lower crustal xenoliths from the Transition Zone in Arizona between the southern Basin and Range Province and the Colorado Plateau. This xenolith suite erupted within a ~25 Ma volcanic host and is dominated by garnet pyroxenite with minor gabbro and amphibolite. Major and trace element geochemistry, petrography, and thermobarometry suggest these rocks represent deep-seated (12-25 kb) cumulates formed during arc magmatism. A preliminary U-Pb sphene age of ~50 Ma suggests that the cumulates formed during the end of the Laramide orogeny. Calculated compositional densities for these cumulates are up to 10% greater than the mantle, suggesting that early to mid-Tertiary arc magmatism generated a dense and unstable lower crustal root. Because these rocks are cold (580-840 °C), thermal contraction may further increase the density contrast. Foundering of this dense root could cause significant uplift. Isostatic calculations show that two kilometers of uplift may be explained by removal of a 20-km-thick root that is 10% denser than the underlying mantle. If lower crustal foundering is indeed responsible for uplift of the Colorado Plateau, the eruption age of the xenolith suite constrains uplift to be younger than ~25 Ma.

  15. Earth Day Then and Now: Reflections by its founder

    SciTech Connect

    Nelson, G.

    1990-04-01

    In this address, the founder of Earth Day recalls the environmental issues of twenty years ago compared to those of this year's observance. He suggests that the two superpowers cut defense spending by 50% this decade and 50% in the next decade, using some of the savings to reverse and restore global environmental damage. He also suggests that the world, and especially the United States, must reduce its reliance on oil and develop solar and other renewable energy technologies. Finally, it was emphasized that waste disposal habits must be changed.

  16. An ancient founder mutation in PROKR2 impairs human reproduction.

    PubMed

    Avbelj Stefanija, Magdalena; Jeanpierre, Marc; Sykiotis, Gerasimos P; Young, Jacques; Quinton, Richard; Abreu, Ana Paula; Plummer, Lacey; Au, Margaret G; Balasubramanian, Ravikumar; Dwyer, Andrew A; Florez, Jose C; Cheetham, Timothy; Pearce, Simon H; Purushothaman, Radhika; Schinzel, Albert; Pugeat, Michel; Jacobson-Dickman, Elka E; Ten, Svetlana; Latronico, Ana Claudia; Gusella, James F; Dode, Catherine; Crowley, William F; Pitteloud, Nelly

    2012-10-01

    Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.

  17. Founder effects initiated rapid species radiation in Hawaiian cave planthoppers.

    PubMed

    Wessel, Andreas; Hoch, Hannelore; Asche, Manfred; von Rintelen, Thomas; Stelbrink, Björn; Heck, Volker; Stone, Fred D; Howarth, Francis G

    2013-06-01

    The Hawaiian Islands provide the venue of one of nature's grand experiments in evolution. Here, we present morphological, behavioral, genetic, and geologic data from a young subterranean insect lineage in lava tube caves on Hawai'i Island. The Oliarus polyphemus species complex has the potential to become a model for studying rapid speciation by stochastic events. All species in this lineage live in extremely similar environments but show strong differentiation in behavioral and morphometric characters, which are random with respect to cave age and geographic distribution. Our observation that phenotypic variability within populations decreases with increasing cave age challenges traditional views on founder effects. Furthermore, these cave populations are natural replicates that can be used to test the contradictory hypotheses. Moreover, Hawaiian cave planthoppers exhibit one of the highest speciation rates among animals and, thus, radically shift our perception on the evolutionary potential of obligate cavernicoles.

  18. Synthetic biology: evolution or revolution? A co-founder's perspective.

    PubMed

    Gardner, Timothy S; Hawkins, Kristy

    2013-12-01

    In this article, we relate the story of Synthetic Biology's birth, from the perspective of a co-founder, and consider its original premise--that standardization and abstraction of biological components will unlock the full potential of biological engineering. The standardization ideas of Synthetic Biology emerged in the late 1990s from a convergence of research on cellular computing, and were motivated by an array of applications from tissue regeneration to bio-sensing to mathematical programming. As the definition of Synthetic Biology has grown to be synonymous with Biological Engineering and Biotechnology, the field has lost sight of the fact that its founding premise has not yet been validated. While the value of standardization has been proven in many other engineering disciplines, none of them involve self-replicating systems. The engineering of self-replicating systems will likely benefit from standardization, and also by embracing the forces of evolution that inexorably shape such systems.

  19. Origins, admixture and founder lineages in European Roma.

    PubMed

    Martínez-Cruz, Begoña; Mendizabal, Isabel; Harmant, Christine; de Pablo, Rosario; Ioana, Mihai; Angelicheva, Dora; Kouvatsi, Anastasia; Makukh, Halyna; Netea, Mihai G; Pamjav, Horolma; Zalán, Andrea; Tournev, Ivailo; Marushiakova, Elena; Popov, Vesselin; Bertranpetit, Jaume; Kalaydjieva, Luba; Quintana-Murci, Lluis; Comas, David

    2016-06-01

    The Roma, also known as 'Gypsies', represent the largest and the most widespread ethnic minority of Europe. There is increasing evidence, based on linguistic, anthropological and genetic data, to suggest that they originated from the Indian subcontinent, with subsequent bottlenecks and undetermined gene flow from/to hosting populations during their diaspora. Further support comes from the presence of Indian uniparentally inherited lineages, such as mitochondrial DNA M and Y-chromosome H haplogroups, in a significant number of Roma individuals. However, the limited resolution of most genetic studies so far, together with the restriction of the samples used, have prevented the detection of other non-Indian founder lineages that might have been present in the proto-Roma population. We performed a high-resolution study of the uniparental genomes of 753 Roma and 984 non-Roma hosting European individuals. Roma groups show lower genetic diversity and high heterogeneity compared with non-Roma samples as a result of lower effective population size and extensive drift, consistent with a series of bottlenecks during their diaspora. We found a set of founder lineages, present in the Roma and virtually absent in the non-Roma, for the maternal (H7, J1b3, J1c1, M18, M35b, M5a1, U3, and X2d) and paternal (I-P259, J-M92, and J-M67) genomes. This lineage classification allows us to identify extensive gene flow from non-Roma to Roma groups, whereas the opposite pattern, although not negligible, is substantially lower (up to 6.3%). Finally, the exact haplotype matching analysis of both uniparental lineages consistently points to a Northwestern origin of the proto-Roma population within the Indian subcontinent. PMID:26374132

  20. Native American Admixture in the Quebec Founder Population

    PubMed Central

    Moreau, Claudia; Lefebvre, Jean-François; Jomphe, Michèle; Bhérer, Claude; Ruiz-Linares, Andres; Vézina, Hélène; Roy-Gagnon, Marie-Hélène; Labuda, Damian

    2013-01-01

    For years, studies of founder populations and genetic isolates represented the mainstream of genetic mapping in the effort to target genetic defects causing Mendelian disorders. The genetic homogeneity of such populations as well as relatively homogeneous environmental exposures were also seen as primary advantages in studies of genetic susceptibility loci that underlie complex diseases. European colonization of the St-Lawrence Valley by a small number of settlers, mainly from France, resulted in a founder effect reflected by the appearance of a number of population-specific disease-causing mutations in Quebec. The purported genetic homogeneity of this population was recently challenged by genealogical and genetic analyses. We studied one of the contributing factors to genetic heterogeneity, early Native American admixture that was never investigated in this population before. Consistent admixture estimates, in the order of one per cent, were obtained from genome-wide autosomal data using the ADMIXTURE and HAPMIX software, as well as with the fastIBD software evaluating the degree of the identity-by-descent between Quebec individuals and Native American populations. These genomic results correlated well with the genealogical estimates. Correlations are imperfect most likely because of incomplete records of Native founders’ origin in genealogical data. Although the overall degree of admixture is modest, it contributed to the enrichment of the population diversity and to its demographic stratification. Because admixture greatly varies among regions of Quebec and among individuals, it could have significantly affected the homogeneity of the population, which is of importance in mapping studies, especially when rare genetic susceptibility variants are in play. PMID:23776491

  1. Founders' Sensemaking and Sensegiving Behaviors Effect on the Organizational Identities of New Charter Schools

    ERIC Educational Resources Information Center

    Fehsenfeld, Corie

    2010-01-01

    This qualitative, multiple case study looked at the emerging organizational identity of four charter schools during the early years of development and the influence of the founder on that developing identity. The study looked at the ways in which each founder's sensemaking and sensegiving behaviors may have influenced the organizational identity…

  2. Identification of kin structure among Guam rail founders: a comparison of pedigrees and DNA profiles

    USGS Publications Warehouse

    Haig, Susan M.; Ballou, J.D.; Casna, N.J.

    1994-01-01

    Kin structure among founders can have a significant effect on subsequent population structure. Here we use the correlation between DNA profile similarity and relatedness calculated from pedigrees to test hypotheses regarding kin structure among founders to the captive Guam rail (Rallus owstoni) population. Five different pedigrees were generated under the following hypotheses: (i) founders are unrelated; (ii) founders are unrelated except for same-nest chicks; (iii) founders from the same major site are siblings; (iv) founders from the same local site are siblings; and (v) founders are related as defined by a UPGMA cluster analysis of DNA similarity data. Relatedness values from pedigrees 1, 2 and 5 had the highest correlation with DNA similarity but the correlation between relatedness and similarity were not significantly different among pedigrees. Pedigree 5 resulted in the highest correlation overall when using only relatedness values that changed as a result of different founder hypotheses. Thus, founders were assigned relatedness based on pedigree 5 because it had the highest correlations with DNA similarity, was the most conservative approach, and incorporated all field data. The analyses indicated that estimating relatedness using DNA profiles remains problematic, therefore we compared mean kinship, a measure of genetic importance, with mean DNA profile similarity to determine if genetic importance among individuals could be determined via use of DNA profiles alone. The significant correlation suggests this method may provide more information about population structure than was previously thought. Thus, DNA profiles can provide a reasonable explanation for founder relatedness and mean DNA profile similarity may be helpful in determining relative genetic importance of individuals when detailed pedigrees are absent.

  3. Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene

    PubMed Central

    Khadilkar, Satish V.; Chaudhari, Chetan R.; Dastur, Rashna S.; Gaitonde, Pradnya S.; Yadav, Jayendra G.

    2016-01-01

    Background and Purpose: Diagnostic evaluation of limb-girdle muscular dystrophy type 2A (LGMD2A) involves specialized studies on muscle biopsy and mutation analysis. Mutation screening is the gold standard for diagnosis but is difficult as the gene is large and multiple mutations are known. This study evaluates the utility of two known founder mutations as a first-line diagnostic test for LGMD2A in the Agarwals. Materials and Methods: The Agarwals with limb-girdle muscular dystrophy (LGMD) phenotype were analyzed for two founder alleles (intron 18/exon 19 c.2051-1G>T and exon 22 c.2338G>C). Asymptomatic first-degree relatives of patients with genetically confirmed mutations and desirous of counseling were screened for founder mutations. Results: Founder alleles were detected in 26 out of 29 subjects with LGMD phenotype (89%). The most common genotype observed was homozygous for exon 22 c.2338 G>C mutation followed by compound heterozygosity. Single founder allele was identified in two. Single allele was detected in two of the five asymptomatic relatives. Conclusion: Eighty-nine percent of the Agarwals having LGMD phenotype have LGMD2A resulting from founder mutations. Founder allele analysis can be utilized as the initial noninvasive diagnostic step for index cases, carrier detection, and counseling. PMID:27011640

  4. Mediterranean Founder Mutation Database (MFMD): Taking Advantage from Founder Mutations in Genetics Diagnosis, Genetic Diversity and Migration History of the Mediterranean Population.

    PubMed

    Charoute, Hicham; Bakhchane, Amina; Benrahma, Houda; Romdhane, Lilia; Gabi, Khalid; Rouba, Hassan; Fakiri, Malika; Abdelhak, Sonia; Lenaers, Guy; Barakat, Abdelhamid

    2015-11-01

    The Mediterranean basin has been the theater of migration crossroads followed by settlement of several societies and cultures in prehistoric and historical times, with important consequences on genetic and genomic determinisms. Here, we present the Mediterranean Founder Mutation Database (MFMD), established to offer web-based access to founder mutation information in the Mediterranean population. Mutation data were collected from the literature and other online resources and systematically reviewed and assembled into this database. The information provided for each founder mutation includes DNA change, amino-acid change, mutation type and mutation effect, as well as mutation frequency and coalescence time when available. Currently, the database contains 383 founder mutations found in 210 genes related to 219 diseases. We believe that MFMD will help scientists and physicians to design more rapid and less expensive genetic diagnostic tests. Moreover, the coalescence time of founder mutations gives an overview about the migration history of the Mediterranean population. MFMD can be publicly accessed from http://mfmd.pasteur.ma.

  5. Expanding the Spectrum of Founder Mutations Causing Isolated Gonadotropin-Releasing Hormone Deficiency

    PubMed Central

    Choi, Jin-Ho; Balasubramanian, Ravikumar; Lee, Phil H.; Shaw, Natalie D.; Hall, Janet E.; Plummer, Lacey; Buck, Cassandra L.; Kottler, Marie-Laure; Jarzabek, Katarzyna; Wołczynski, Sławomir; Quinton, Richard; Latronico, Ana Claudia; Dode, Catherine; Ogata, Tsutomu; Kim, Hyung-Goo; Layman, Lawrence C.; Gusella, James F.

    2015-01-01

    Context: Loss of function (LoF) mutations in more than 20 genes are now known to cause isolated GnRH deficiency (IGD) in humans. Most causal IGD mutations are typically private, ie, limited to a single individual/pedigree. However, somewhat paradoxically, four IGD genes (GNRH1, TAC3, PROKR2, and GNRHR) have been shown to harbor LoF founder mutations that are shared by multiple unrelated individuals. It is not known whether similar founder mutations occur in other IGD genes. Objective: The objective of the study was to determine whether shared deleterious mutations in IGD-associated genes represent founder alleles. Setting: This study was an international collaboration among academic medical centers. Methods: IGD patients with shared mutations, defined as those documented in three or more unrelated probands in 14 IGD-associated genes, were identified from various academic institutions, the Human Gene Mutation Database, and literature reports by other international investigators. Haplotypes of single-nucleotide polymorphisms and short tandem repeats surrounding the mutations were constructed to assess genetic ancestry. Results: A total of eight founder mutations in five genes, GNRHR (Q106R, R262Q, R139H), TACR3 (W275X), PROKR2 (R85H), FGFR1 (R250Q, G687R), and HS6ST1 (R382W) were identified. Most founder alleles were present at low frequency in the general population. The estimated age of these mutant alleles ranged from 1925 to 5600 years and corresponded to the time of rapid human population expansion. Conclusions: We have expanded the spectrum of founder alleles associated with IGD to a total of eight founder mutations. In contrast to the approximately 9000-year-old PROKR2 founder allele that may confer a heterozygote advantage, the rest of the founder alleles are relatively more recent in origin, in keeping with the timing of recent human population expansion and any selective heterozygote advantage of these alleles requires further evaluation. PMID:26207952

  6. Genetic Comparison of a Croatian Isolate and CEPH European Founders

    PubMed Central

    Navarro, Pau; Vitart, Véronique; Hayward, Caroline; Tenesa, Albert; Zgaga, Lina; Juricic, Danica; Polasek, Ozren; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Wright, Alan F; Haley, Chris S; Knott, Sara A

    2010-01-01

    Human isolates have been postulated as a good resource for the identification of QTL due to reduced genetic diversity and a more homogeneous environment. Isolates may also have increased linkage disequilibrium (LD) due to small effective population size and, either loss or increase in frequency of alleles that are rare in the general population from which they originate. Here we investigate the difference in allele and genotype frequencies, LD and homozygous tracts between an isolate—several villages from the island of Vis in Croatia—and an outbred population of European origin: the Hapmap CEPH founders. Using the HumanHap300 v1 Genotyping BeadChip, we show that our population does not differ greatly from the reference CEU outbred population despite having a slightly higher proportion of monomorphic loci, a slightly higher long-range LD, and a greater proportion of individuals with long homozygous tracts. We conclude that genotyping arrays should perform equally well in our isolate as in outbred European populations for disease mapping studies and that SNP–trait associations discovered in our well-characterized Croatian isolate should be valid in the general European population from which they descend. Genet. Epidemiol. 34: 140–145, 2010. © 2009 Wiley-Liss, Inc. PMID:19697321

  7. Ludwig Edinger (1855-1918): founder of modern neuroanatomy.

    PubMed

    Prithishkumar, Ivan James

    2012-03-01

    Ludwig Edinger, a German neurologist is considered as one of the founders of modern neuroanatomy. He was conferred the degree of Doctor of Medicine at the University of Strassburg. His observation of small living organisms under a microscope at an early age led him to study medicine. Edinger had many discoveries to his credit. He was the first to describe the ventral and dorsal spinocerebellar tracts, to distinguish between paleo-encephalon and neo-encephalon, and between paleo-cerebellum and neo-cerebellum. He coined the terms "gnosis" and "praxis," which were later adopted in psychological descriptions of agnosia and apraxia. He identified the Edinger-Westphal nucleus in 1885 and was the first to describe the syndrome of thalamic pain. Edinger worked with renowned clinicians and published a large number of papers. He founded the Neurological Institute at the Goethe University in Frankfurt, which is the oldest neurological Institute in Germany. Edinger was a rare combination of a profound scientist, a brilliant teacher, a fine artist, and a noted hypnotist. While at the height of his career, he underwent a surgery and died a few hours later. It was his last will that his brain should be dissected in his own institute. It showed extraordinarily well-developed occipital lobes as well as other unusual features. PMID:21800368

  8. Long-distance plant dispersal to North Atlantic islands: colonization routes and founder effect

    PubMed Central

    Alsos, Inger Greve; Ehrich, Dorothee; Eidesen, Pernille Bronken; Solstad, Heidi; Westergaard, Kristine Bakke; Schönswetter, Peter; Tribsch, Andreas; Birkeland, Siri; Elven, Reidar; Brochmann, Christian

    2015-01-01

    Long-distance dispersal (LDD) processes influence the founder effect on islands. We use genetic data for 25 Atlantic species and similarities among regional floras to analyse colonization, and test whether the genetic founder effect on five islands is associated with dispersal distance, island size and species traits. Most species colonized postglacially via multiple dispersal events from several source regions situated 280 to >3000 km away, and often not from the closest ones. A strong founder effect was observed for insect-pollinated mixed maters, and it increased with dispersal distance and decreased with island size in accordance with the theory of island biogeography. Only a minor founder effect was observed for wind-pollinated outcrossing species. Colonization patterns were largely congruent, indicating that despite the importance of stochasticity, LDD is mainly determined by common factors, probably dispersal vectors. Our findings caution against a priori assuming a single, close source region in biogeographic analyses. PMID:25876627

  9. Genetic Studies of Stuttering in a Founder Population

    PubMed Central

    Wittke-Thompson, Jacqueline K.; Ambrose, Nicoline; Yairi, Ehud; Roe, Cheryl; Cook, Edwin H.; Ober, Carole; Cox, Nancy J.

    2007-01-01

    Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180–195 cM) and 5 (P=0.0051, 105–120 cM; P=0.015, 120–135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta-analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. PMID:17276504

  10. Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

    PubMed Central

    2012-01-01

    Background Tunisia is a North African country of 10 million inhabitants. The native background population is Berber. However, throughout its history, Tunisia has been the site of invasions and migratory waves of allogenic populations and ethnic groups such as Phoenicians, Romans, Vandals, Arabs, Ottomans and French. Like neighbouring and Middle Eastern countries, the Tunisian population shows a relatively high rate of consanguinity and endogamy that favor expression of recessive genetic disorders at relatively high rates. Many factors could contribute to the recurrence of monogenic morbid trait expression. Among them, founder mutations that arise in one ancestral individual and diffuse through generations in isolated communities. Method We report here on founder mutations in the Tunisian population by a systematic review of all available data from PubMed, other sources of the scientific literature as well as unpublished data from our research laboratory. Results We identified two different classes of founder mutations. The first includes founder mutations so far reported only among Tunisians that are responsible for 30 genetic diseases. The second group represents founder haplotypes described in 51 inherited conditions that occur among Tunisians and are also shared with other North African and Middle Eastern countries. Several heavily disabilitating diseases are caused by recessive founder mutations. They include, among others, neuromuscular diseases such as congenital muscular dystrophy and spastic paraglegia and also severe genodermatoses such as dystrophic epidermolysis bullosa and xeroderma pigmentosa. Conclusion This report provides informations on founder mutations for 73 genetic diseases either specific to Tunisians or shared by other populations. Taking into account the relatively high number and frequency of genetic diseases in the region and the limited resources, screening for these founder mutations should provide a rapid and cost effective tool for

  11. Identification of a founder mutation for maple syrup urine disease in Hutterites.

    PubMed

    Mroch, Amelia; Davis-Keppen, Laura; Matthes, Cindy; Stein, Quinn

    2014-04-01

    Maple syrup urine disease (MSUD) is an organic acidemia detected on newborn screening. The condition has been reported with increased frequency in certain founder populations including Hutterites. We present a case of MSUD in a Hutterite boy. Mutation analysis was completed and identified a candidate founder mutation in the BCKDHB gene, specifically c.595_596delAG. Further testing of other Hutterites with MSUD is needed to determine whether additional mutations may exist. PMID:24791375

  12. Legacy of mutiny on the Bounty: founder effect and admixture on Norfolk Island

    PubMed Central

    Macgregor, Stuart; Bellis, Claire; Lea, Rod A; Cox, Hannah; Dyer, Tom; Blangero, John; Visscher, Peter M; Griffiths, Lyn R

    2010-01-01

    The population of Norfolk Island, located off the eastern coast of Australia, possesses an unusual and fascinating history. Most present-day islanders are related to a small number of the ‘Bounty' mutineer founders. These founders consisted of Caucasian males and Polynesian females and led to an admixed present-day population. By examining a single large pedigree of 5742 individuals, spanning >200 years, we analyzed the influence of admixture and founder effect on various cardiovascular disease (CVD)-related traits. On account of the relative isolation of the population, on average one-third of the genomes of present-day islanders (single large pedigree individuals) is derived from 17 initial founders. The proportion of Polynesian ancestry in the present-day individuals was found to significantly influence total triglycerides, body mass index, systolic blood pressure and diastolic blood pressure. For various cholesterol traits, the influence of ancestry was less marked but overall the direction of effect for all CVD-related traits was consistent with Polynesian ancestry conferring greater CVD risk. Marker-derived homozygosity was computed and agreed with measures of inbreeding derived from pedigree information. Founder effect (inbreeding and marker-derived homozygosity) significantly influenced height. In conclusion, both founder effect and extreme admixture have substantially influenced the genetic architecture of a variety of CVD-related traits in this population. PMID:19584896

  13. New insights on lithospheric foundering from thermo-mechanically coupled numerical modelling

    NASA Astrophysics Data System (ADS)

    Pastor-Galán, Daniel; Thieulot, Cedric

    2015-04-01

    Earth's lithosphere is recycled into the mantle as required by global mass considerations. At least during the latest 1 G.y. the main mechanism of lithospheric foundering into the mantle has been subduction. Yet other mechanisms of mantle removal such as Rayleigh-Taylor-type instability or delamination have significant influence at present as revealed by mantle anomalies, and are considered to be likely candidates for the main recycling mechanisms of lithospheric during the Archean. Although lithospheric mantle removal has been geophysically imaged, e.g. Carpathians, Colorado Plateau, at many other locations geophysical and geological observations also seem to indicate that mantle lithosphere is anomalously thin or absent. Potential places where lithospheric mantle foundering processes took place are The Urals, the Variscides, underneath the Ibero Armorican Orocline in western Europe, and the Tibetan, Puna and Anatolian Plateaus. Lithospheric foundering has been blamed for, among others, cratonization processes, rapid surface uplift, generation of voluminous magmatism, changes in crustal stress from compression to extension and a long etc. However, its triggering mechanisms are not well studied, and a variety of possible explanations have been given for lithospheric foundering processes, including convective instability following orogenic thickening or some other perturbation of thermal boundary layers, development of eclogitic roots, erosion of the lithosphere by a flat-subducting slab or partial melting of the asthenosphere, and partial intruding pyroxenites into the base of lithosphere. To understand the mechanisms, causes and consequences of lithospheric foundering, we explored lithospheric foundering in an assortment of scenarios using the numerical code, ELEFANT, an user-friendly multipurpose geodynamics code. Preliminary results indicate that changes in geometry, thermal state and composition of the lithosphere, associated with mantle flow, can have a first

  14. Analysis of founder-specific inbreeding depression on birth weight in Ripollesa lambs.

    PubMed

    Casellas, J; Piedrafita, J; Caja, G; Varona, L

    2009-01-01

    Although inbreeding (F) is a topic of major concern in animal breeding, estimates of inbreeding depression are usually obtained by modeling the overall F coefficient of each individual, without considering that the recessive (deleterious) genetic load of a given population may be unevenly distributed among the founder genomes. The founder-specific partial F coefficient is calculated as the identity-by-descent probability at any given autosomal locus related to a particular founder and allows a more detailed analysis of inbreeding depression on productive traits. Within this context, birth BW data from 2,459 Ripollesa lambs were analyzed under a hierarchical animal model without F-related covariates (model 0), with inbreeding depression modeled by the overall F coefficient (model F1), or by the partial F coefficient of 9 founders that made a relevant contribution to the population inbreeding (model F2). A straightforward empirical Bayes factor (BF) was developed for testing statistical relevance of each F-related covariate, in which greater-than-1 values favored the model including the covariate. The deviance information criterion (DIC) clearly supported model F1 (5,767.8) rather than model 0 (5,771.2), suggesting that inbreeding depression had a relevant influence on birth BW data. The linear effect of inbreeding depression was statistically relevant in model F1 (BF = 2.52 x 10(35)), with lamb birth BW declining by -13.6 g with each 1% F increase. The quadratic effect of inbreeding depression was almost null in model F1 (BF = 0.02), as suggested by the reduction in DIC (5,766.9) when this effect was removed from model F1. On the other hand, model F2 provided a similar DIC (5,767.9) value, with this parameter decreasing to 5,764.7 when nonrelevant founder-specific inbreeding depression effects were removed. Substantial heterogeneity in founder-specific inbreeding depression was reported by model F2, in which estimates for 4 of the 9 founders did not differ from zero

  15. Interpretation of findings of founder population genetics studies applying lineage extinction theory

    NASA Astrophysics Data System (ADS)

    Livni, Haim; Livni, Joseph

    2016-11-01

    Population genetic investigation of founder events produce intriguing results and this work discusses how branching processes help the cross-examination of such results. For example one reads that 40% of the current Ashkenazi population carry the mtDNA of four founding mothers, (Behar et al., 2006) half of the Ashkenazi Levites descend from one founder (Behar et al., 2003), and 22% of the Malagasy population are descendants of a Polynesian ancestor, (Cox et al., 2012). Probability distributions obtained using a Galton-Watson lineage extinction model yield statistical relations between current population and founder population data. These relations lead to most likely estimates and 90% confidence intervals of the founder population size. The investigation compares the Galton-Watson methodology with the Wright-Fisher model adopted by coalescent theory and a back-to-back analysis of the Malagasy founder event produces matching results. The results reconcile the previous knowledge about the roots of Ashkenazi Jewry with published population genetic findings. They also confirm that random drift is sufficient to explain the genetic findings of the examined examples.

  16. Plasmodium falciparum Founder Populations in Western Cambodia Have Reduced Artemisinin Sensitivity In Vitro

    PubMed Central

    Amaratunga, Chanaki; Witkowski, Benoit; Dek, Dalin; Try, Vorleak; Khim, Nimol; Miotto, Olivo

    2014-01-01

    Reduced Plasmodium falciparum sensitivity to short-course artemisinin (ART) monotherapy manifests as a long parasite clearance half-life. We recently defined three parasite founder populations with long half-lives in Pursat, western Cambodia, where reduced ART sensitivity is prevalent. Using the ring-stage survival assay, we show that these founder populations have reduced ART sensitivity in vitro at the early ring stage of parasite development and that a genetically admixed population contains subsets of parasites with normal or reduced ART sensitivity. PMID:24867977

  17. 77 FR 76586 - Founders Equity SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-28

    ... ADMINISTRATION Founders Equity SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Founders Equity SBIC I, L.P., 711 Fifth... Equity SBIC I, L.P. proposes to provide debt security financing to Richardson Foods, Inc., 101 Erie...

  18. 76 FR 35263 - Founders Equity SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Founders Equity SBIC I, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that Founders Equity SBIC I, L.P., 711 Fifth Avenue, 5th Floor, New York, NY 10022,...

  19. Molecular Diagnosis of Hereditary Fructose Intolerance: Founder Mutation in a Community from India.

    PubMed

    Bijarnia-Mahay, Sunita; Movva, Sireesha; Gupta, Neerja; Sharma, Deepak; Puri, Ratna D; Kotecha, Udhaya; Saxena, Renu; Kabra, Madhulika; Mohan, Neelam; Verma, Ishwar C

    2015-01-01

    Hereditary fructose intolerance (HFI) is a difficult-to-confirm diagnosis, requiring either invasive liver biopsy-enzyme assay or potentially hazardous fructose challenge test or expensive molecular genetic analysis. Therefore, worldwide there has been a trend towards finding "common mutations" in distinct ethnic groups to simplify the process of diagnosis. The nonspecific presentation of the disease often leads to diagnostic confusion with other metabolic liver disorders such as glycogenoses, galactosemia, and tyrosinemia. This leads to much delay in diagnosis with consequent harm to the patient.We report mutations in the ALDOB gene, from eleven Indian patients, seven of whom belong to the Agarwal community. Six patients from the Agarwal community and two non-Agarwal patients harbored one novel mutation, c.324+1G>A (five homozygous and one heterozygous), in the ALDOB gene. Haplotyping performed in families confirmed a founder effect. The community has been known to harbor founder mutations in other genes such as the MLC1, PANK2, and CAPN3 genes, thus providing another evidence for a founder effect in the community in case of HFI. This may pave the path for a simpler and quicker test at least for this community in India. In addition to the founder mutation, we report four other novel mutations, c.112+1delG, c.380-1G>A, c.677G>A, and c.689delA, and a previously reported mutation, c.1013C>T, in the cohort from India.

  20. Estimation of Epistatic Variance Components and Heritability in Founder Populations and Crosses

    PubMed Central

    Young, Alexander I.; Durbin, Richard

    2014-01-01

    Genetic association studies have explained only a small proportion of the estimated heritability of complex traits, leaving the remaining heritability “missing.” Genetic interactions have been proposed as an explanation for this, because they lead to overestimates of the heritability and are hard to detect. Whether this explanation is true depends on the proportion of variance attributable to genetic interactions, which is difficult to measure in outbred populations. Founder populations exhibit a greater range of kinship than outbred populations, which helps in fitting the epistatic variance. We extend classic theory to founder populations, giving the covariance between individuals due to epistasis of any order. We recover the classic theory as a limit, and we derive a recently proposed estimator of the narrow sense heritability as a corollary. We extend the variance decomposition to include dominance. We show in simulations that it would be possible to estimate the variance from pairwise interactions with samples of a few thousand from strongly bottlenecked human founder populations, and we provide an analytical approximation of the standard error. Applying these methods to 46 traits measured in a yeast (Saccharomyces cerevisiae) cross, we estimate that pairwise interactions explain 10% of the phenotypic variance on average and that third- and higher-order interactions explain 14% of the phenotypic variance on average. We search for third-order interactions, discovering an interaction that is shared between two traits. Our methods will be relevant to future studies of epistatic variance in founder populations and crosses. PMID:25326236

  1. Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population

    PubMed Central

    Gauvin, Héloïse; Moreau, Claudia; Lefebvre, Jean-François; Laprise, Catherine; Vézina, Hélène; Labuda, Damian; Roy-Gagnon, Marie-Hélène

    2014-01-01

    In genetics the ability to accurately describe the familial relationships among a group of individuals can be very useful. Recent statistical tools succeeded in assessing the degree of relatedness up to 6–7 generations with good power using dense genome-wide single-nucleotide polymorphism data to estimate the extent of identity-by-descent (IBD) sharing. It is therefore important to describe genome-wide patterns of IBD sharing for more remote and complex relatedness between individuals, such as that observed in a founder population like Quebec, Canada. Taking advantage of the extended genealogical records of the French Canadian founder population, we first compared different tools to identify regions of IBD in order to best describe genome-wide IBD sharing and its correlation with genealogical characteristics. Results showed that the extent of IBD sharing identified with FastIBD correlates best with relatedness measured using genealogical data. Total length of IBD sharing explained 85% of the genealogical kinship's variance. In addition, we observed significantly higher sharing in pairs of individuals with at least one inbred ancestor compared with those without any. Furthermore, patterns of IBD sharing and average sharing were different across regional populations, consistent with the settlement history of Quebec. Our results suggest that, as expected, the complex relatedness present in founder populations is reflected in patterns of IBD sharing. Using these patterns, it is thus possible to gain insight on the types of distant relationships in a sample from a founder population like Quebec. PMID:24129432

  2. A. G. Vernon Harcourt: A Founder of Chemical Kinetics and a Friend of "Lewis Carroll."

    ERIC Educational Resources Information Center

    Shorter, John

    1980-01-01

    Outlines the life of A. G. Vernon Harcourt, a founder of chemical kinetics, contributor to the purification of coal gas from sulfur compounds, inventor of the percentage chloroform inhaler, friend to Lewis Carroll, and instructor to the Prince of Wales. (CS)

  3. Optimization methods for selecting founder individuals for captive breeding or reintroduction of endangered species.

    PubMed

    Miller, Webb; Wright, Stephen J; Zhang, Yu; Schuster, Stephan C; Hayes, Vanessa M

    2010-01-01

    Methods from genetics and genomics can be employed to help save endangered species. One potential use is to provide a rational strategy for selecting a population of founders for a captive breeding program. The hope is to capture most of the available genetic diversity that remains in the wild population, to provide a safe haven where representatives of the species can be bred, and eventually to release the progeny back into the wild. However, the founders are often selected based on a random-sampling strategy whose validity is based on unrealistic assumptions. Here we outline an approach that starts by using cutting-edge genome sequencing and genotyping technologies to objectively assess the available genetic diversity. We show how combinatorial optimization methods can be applied to these data to guide the selection of the founder population. In particular, we develop a mixed-integer linear programming technique that identifies a set of animals whose genetic profile is as close as possible to specified abundances of alleles (i.e., genetic variants), subject to constraints on the number of founders and their genders and ages. PMID:19908356

  4. Hallie Quinn Brown (1845-Or 1850-1949): Educator, Author, Lecturer, Founder, and Reformer

    ERIC Educational Resources Information Center

    Evans, A.L.; Lamikanra, A.E.; Jones, O.S.L.; Evans, V.

    2004-01-01

    Most black educators are aware of black pioneers, such as Frederick Douglass, Phillis Wheatley, Booker T. Washington, W. E. B. DuBois, George Washington Carver, Mary McLeod Bethune, and others, Few are, however, aware of Hallie Quinn Brown (1845-or 1850-1949) educator, author, lecture, founder, and reformer, who wrote one of the first biographies…

  5. Teaching Evolution through the Founder Effect: A Standards-Based Activity.

    ERIC Educational Resources Information Center

    Leonard, William H.; Edmondson, Elizabeth

    2003-01-01

    Presents an activity called "The Hardy-Weinberg Equilibrium, Founder Effect, and Evolution" to allow students to learn about evolution in an engaging, constructivist manner. The activity also uses the tools of mathematics to learn several related biology concepts. (Author/SOE)

  6. 171. Credit PG&E. Hamden Holmes Noble, founder of the Keswick ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    171. Credit PG&E. Hamden Holmes Noble, founder of the Keswick Electric Power Company. President of Keswick Power and its successor companies -- Northern California Power Company and Northern California Power Company, Consolidated (until 1915). - Battle Creek Hydroelectric System, Battle Creek & Tributaries, Red Bluff, Tehama County, CA

  7. Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population.

    PubMed

    Gauvin, Héloïse; Moreau, Claudia; Lefebvre, Jean-François; Laprise, Catherine; Vézina, Hélène; Labuda, Damian; Roy-Gagnon, Marie-Hélène

    2014-06-01

    In genetics the ability to accurately describe the familial relationships among a group of individuals can be very useful. Recent statistical tools succeeded in assessing the degree of relatedness up to 6-7 generations with good power using dense genome-wide single-nucleotide polymorphism data to estimate the extent of identity-by-descent (IBD) sharing. It is therefore important to describe genome-wide patterns of IBD sharing for more remote and complex relatedness between individuals, such as that observed in a founder population like Quebec, Canada. Taking advantage of the extended genealogical records of the French Canadian founder population, we first compared different tools to identify regions of IBD in order to best describe genome-wide IBD sharing and its correlation with genealogical characteristics. Results showed that the extent of IBD sharing identified with FastIBD correlates best with relatedness measured using genealogical data. Total length of IBD sharing explained 85% of the genealogical kinship's variance. In addition, we observed significantly higher sharing in pairs of individuals with at least one inbred ancestor compared with those without any. Furthermore, patterns of IBD sharing and average sharing were different across regional populations, consistent with the settlement history of Quebec. Our results suggest that, as expected, the complex relatedness present in founder populations is reflected in patterns of IBD sharing. Using these patterns, it is thus possible to gain insight on the types of distant relationships in a sample from a founder population like Quebec.

  8. Serial founder effects during range expansion: a spatial analog of genetic drift.

    PubMed

    Slatkin, Montgomery; Excoffier, Laurent

    2012-05-01

    Range expansions cause a series of founder events. We show that, in a one-dimensional habitat, these founder events are the spatial analog of genetic drift in a randomly mating population. The spatial series of allele frequencies created by successive founder events is equivalent to the time series of allele frequencies in a population of effective size ke, the effective number of founders. We derive an expression for ke in a discrete-population model that allows for local population growth and migration among established populations. If there is selection, the net effect is determined approximately by the product of the selection coefficients and the number of generations between successive founding events. We use the model of a single population to compute analytically several quantities for an allele present in the source population: (i) the probability that it survives the series of colonization events, (ii) the probability that it reaches a specified threshold frequency in the last population, and (iii) the mean and variance of the frequencies in each population. We show that the analytic theory provides a good approximation to simulation results. A consequence of our approximation is that the average heterozygosity of neutral alleles decreases by a factor of 1-1/(2ke) in each new population. Therefore, the population genetic consequences of surfing can be predicted approximately by the effective number of founders and the effective selection coefficients, even in the presence of migration among populations. We also show that our analytic results are applicable to a model of range expansion in a continuously distributed population.

  9. Momir H. Polenakovic - Founder of the Nephrology Associations in the Republic of Macedonia.

    PubMed

    Spasovski, Goce; Stojceva-Taneva, Olivera

    2015-01-01

    Acad. Momir Polenakovic has devoted his life and work in the diagnosis and treatment of kidney patients, as well as in research of kidney disease. The great experience he has acquired in the work with kidney patients, and after the visit to the most renowned nephrology centers in Europe and the world, he has transferred it to his colleagues through the work in the medical and nephrology associations. The work of the associations was in fact a successful education of young doctors and specialists. Among his most distinguished positions, we can mention: President of the Macedonian Medical Association, founder and President of the MSNDTAO, President of the Yugoslav Society of Nephrology, founder and President of BANTAO, as well as member of the Boards of ESAO and ERA-EDTA. He has received a lot of recognitions for his work achievements. PMID:27442373

  10. The legacy of nuclear risk and the founder effect in biotechnology organizations.

    PubMed

    Fleising, Usher

    2002-04-01

    In the wake of the Chernobyl nuclear accident and a decline in the public trust of science, the founders of modern biotechnology recognized the strategic importance of risk assessment and regulatory affairs. In an effort to avoid the demonization that was attached to the nuclear industry, the pioneers of modern biotechnology delegated authority for regulatory negotiation and risk management to senior positions in the firm. At the same time, the Biotechnology Industry Organization was handed great latitude and trust with making public pronouncements on issues of bioethics and public policy. The way in which founders and leaders embed norms for negotiating regulation and responding to public perceptions has proved important in the maturation and acceptance of a biotechnology sector. PMID:11906747

  11. [Biography and bibliography of Francesco Fede, the founder of Italian pediatrics].

    PubMed

    Farnetani, F; Navarra, A; Farnetani, I

    2011-12-01

    For the first time, an overall study of the life and works of Francesco Fede, the founder of Italian pediatrics, has been carried out. Unpublished biographical data was collected and the complete bibliographic works of Fede were presented. Fede is the hallmark of both scientific matter, which reached a climax in the definition of the Riga and Fede illness, and for his disinterested dedication as a Member of Parliament to foster development in didactics, research and assistance for pediatrics.

  12. Subspecies composition and founder contribution of the captive U.S. chimpanzee (Pan troglodytes) population.

    PubMed

    Ely, John J; Dye, Brent; Frels, William I; Fritz, Jo; Gagneux, Pascal; Khun, Henry H; Switzer, William M; Lee, D Rick

    2005-10-01

    Chimpanzees are presently classified into three subspecies: Pan troglodytes verus from west Africa, P.t. troglodytes from central Africa, and P.t. schweinfurthii from east Africa. A fourth subspecies (P.t. vellerosus), from Cameroon and northern Nigeria, has been proposed. These taxonomic designations are based on geographical origins and are reflected in sequence variation in the first hypervariable region (HVR-I) of the mtDNA D-loop. Although advances have been made in our understanding of chimpanzee phylogenetics, little has been known regarding the subspecies composition of captive chimpanzees. We sequenced part of the mtDNA HVR-I region in 218 African-born population founders and performed a phylogenetic analysis with previously characterized African sequences of known provenance to infer subspecies affiliations. Most founders were P.t. verus (95.0%), distantly followed by the troglodytes schweinfurthii clade (4.6%), and a single P.t. vellerosus (0.4%). Pedigree-based estimates of genomic representation in the descendant population revealed that troglodytes schweinfurthii founder representation was reduced in captivity, vellerosus representation increased due to prolific breeding by a single male, and reproductive variance resulted in uneven representation among male P.t.verus founders. No increase in mortality was evident from between-subspecies interbreeding, indicating a lack of outbreeding depression. Knowledge of subspecies and their genomic representation can form the basis for phylogenetically informed genetic management of extant chimpanzees to preserve rare genetic variation for research, conservation, or possible future breeding. PMID:16229023

  13. Proof-of-principle rapid noninvasive prenatal diagnosis of autosomal recessive founder mutations

    PubMed Central

    Zeevi, David A.; Altarescu, Gheona; Weinberg-Shukron, Ariella; Zahdeh, Fouad; Dinur, Tama; Chicco, Gaya; Herskovitz, Yair; Renbaum, Paul; Elstein, Deborah; Levy-Lahad, Ephrat; Rolfs, Arndt; Zimran, Ari

    2015-01-01

    BACKGROUND. Noninvasive prenatal testing can be used to accurately detect chromosomal aneuploidies in circulating fetal DNA; however, the necessity of parental haplotype construction is a primary drawback to noninvasive prenatal diagnosis (NIPD) of monogenic disease. Family-specific haplotype assembly is essential for accurate diagnosis of minuscule amounts of circulating cell-free fetal DNA; however, current haplotyping techniques are too time-consuming and laborious to be carried out within the limited time constraints of prenatal testing, hampering practical application of NIPD in the clinic. Here, we have addressed this pitfall and devised a universal strategy for rapid NIPD of a prevalent mutation in the Ashkenazi Jewish (AJ) population. METHODS. Pregnant AJ couples, carrying mutation(s) in GBA, which encodes acid β-glucosidase, were recruited at the SZMC Gaucher Clinic. Targeted next-generation sequencing of GBA-flanking SNPs was performed on peripheral blood samples from each couple, relevant mutation carrier family members, and unrelated individuals who are homozygotes for an AJ founder mutation. Allele-specific haplotypes were constructed based on linkage, and a consensus Gaucher disease–associated founder mutation–flanking haplotype was fine mapped. Together, these haplotypes were used for NIPD. All test results were validated by conventional prenatal or postnatal diagnostic methods. RESULTS. Ten parental alleles in eight unrelated fetuses were diagnosed successfully based on the noninvasive method developed in this study. The consensus mutation–flanking haplotype aided diagnosis for 6 of 9 founder mutation alleles. CONCLUSIONS. The founder NIPD method developed and described here is rapid, economical, and readily adaptable for prenatal testing of prevalent autosomal recessive disease-causing mutations in an assortment of worldwide populations. FUNDING. SZMC, Protalix Biotherapeutics Inc., and Centogene AG. PMID:26426075

  14. Twin Town in South Brazil: a Nazi's experiment or a genetic founder effect?

    PubMed

    Tagliani-Ribeiro, Alice; Oliveira, Mariana; Sassi, Adriana K; Rodrigues, Maira R; Zagonel-Oliveira, Marcelo; Steinman, Gary; Matte, Ursula; Fagundes, Nelson J R; Schuler-Faccini, Lavinia

    2011-01-01

    Cândido Godói (CG) is a small municipality in South Brazil with approximately 6,000 inhabitants. It is known as the "Twins' Town" due to its high rate of twin births. Recently it was claimed that such high frequency of twinning would be connected to experiments performed by the German Nazi doctor Joseph Mengele. It is known, however, that this town was founded by a small number of families and therefore a genetic founder effect may represent an alternatively explanation for the high twinning prevalence in CG. In this study, we tested specific predictions of the "Nazi's experiment" and of the "founder effect" hypotheses. We surveyed a total of 6,262 baptism records from 1959-2008 in CG catholic churches, and identified 91 twin pairs and one triplet. Contrary to the "Nazi's experiment hypothesis", there is no spurt in twinning between the years (1964-1968) when Mengele allegedly was in CG (P = 0.482). Moreover, there is no temporal trend for a declining rate of twinning since the 1960s (P = 0.351), and no difference in twinning among CG districts considering two different periods: 1927-1958 and 1959-2008 (P = 0.638). On the other hand, the "founder effect hypothesis" is supported by an isonymy analysis that shows that women who gave birth to twins have a higher inbreeding coefficient when compared to women who never had twins (0.0148, 0.0081, respectively, P = 0.019). In summary, our results show no evidence for the "Nazi's experiment hypothesis" and strongly suggest that the "founder effect hypothesis" is a much more likely alternative for explaining the high prevalence of twinning in CG. If this hypothesis is correct, then this community represents a valuable population where genetic factors linked to twinning may be identified.

  15. The contribution of founder mutations in BRCA1 to breast cancer in Belarus.

    PubMed

    Uglanitsa, N; Oszurek, O; Uglanitsa, K; Savonievich, E; Lubiński, J; Cybulski, C; Debniak, T; Narod, S A; Gronwald, J

    2010-10-01

    Mutations in the BRCA1 gene increase susceptibility to both breast and ovarian cancer. In some countries, including several in Eastern Europe, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases. To estimate the hereditary proportion of breast cancer in Belarus, we sought the presence of any of three founder mutations in BRCA1 (4153delA, 5382insC and C61G) in 500 unselected cases of breast cancer. These mutations have previously been identified in breast/ovarian cancer families from Belarus and from other Slavic countries, including Poland and Russia. One of the three founder mutations in BRCA1 was present in 38 of 500 unselected cases of breast cancer (7.6%). A mutation was found in 12.6% of women diagnosed before age 50 and 5.6% of women diagnosed after age 50. A mutation was identified in 2 of 251 newborn controls (0.8%). The hereditary proportion of breast cancers in Belarus is among the highest of any countries studied to date.

  16. Identification of a founder BRCA1 mutation in the Moroccan population.

    PubMed

    Quiles, F; Teulé, À; Martinussen Tandstad, N; Feliubadaló, L; Tornero, E; Del Valle, J; Menéndez, M; Salinas, M; Wethe Rognlien, V; Velasco, A; Izquierdo, A; Capellá, G; Brunet, J; Lázaro, C

    2016-10-01

    Breast cancer (BC) is the most frequent cancer among women in Morocco. However, the role of the most prevalent BC-predisposing genes, BRCA1 and BRCA2, has been largely unexplored. To help define the role of BRCA1 in BC in Morocco, we characterized the first potential BRCA1 founder mutation in this population. Genetic testing of BRCA1 and BRCA2 in BC high-risk families identified mutation BRCA1 c.5309G>T, p.(Gly1770Val) or G1770V in five independent families from Morocco, suggesting a founder effect. To confirm this hypothesis, haplotype construction was performed using seven intragenic and flanking BRCA1 microsatellite markers. Clinical data were also compiled. Clinical data from carriers of mutation G1770V correspond to data from carriers of BRCA1 pathogenic mutations. Microsatellite analysis showed a common haplotype for the five families in a region comprising 1.54 Mb, confirming G1770V as the first specific founder BRCA1 mutation in the Moroccan population. Our findings contribute to a better understanding of BC genetics in the Moroccan population. Nevertheless, comprehensive studies of mutation G1770V in large series of BC patients from Morocco are needed to assess the real prevalence of this mutation and to improve genetic testing and risk assessment in this population.

  17. A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats.

    PubMed

    Ferrando, A; Manunza, A; Jordana, J; Capote, J; Pons, A; Pais, J; Delgado, T; Atoche, P; Cabrera, B; Martínez, A; Landi, V; Delgado, J V; Argüello, A; Vidal, O; Lalueza-Fox, C; Ramírez, O; Amills, M

    2015-08-01

    In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island. PMID:26153924

  18. Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus

    PubMed Central

    Tully, Damien C.; Ogilvie, Colin B.; Batorsky, Rebecca E.; Bean, David J.; Power, Karen A.; Ghebremichael, Musie; Bedard, Hunter E.; Gladden, Adrianne D.; Seese, Aaron M.; Amero, Molly A.; Lane, Kimberly; McGrath, Graham; Bazner, Suzane B.; Tinsley, Jake; Lennon, Niall J.; Henn, Matthew R.; Brumme, Zabrina L.; Norris, Philip J.; Rosenberg, Eric S.; Mayer, Kenneth H.; Jessen, Heiko; Kosakovsky Pond, Sergei L.; Walker, Bruce D.; Altfeld, Marcus; Carlson, Jonathan M.; Allen, Todd M.

    2016-01-01

    Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic “signatures” within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission. PMID:27163788

  19. Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

    PubMed

    Tully, Damien C; Ogilvie, Colin B; Batorsky, Rebecca E; Bean, David J; Power, Karen A; Ghebremichael, Musie; Bedard, Hunter E; Gladden, Adrianne D; Seese, Aaron M; Amero, Molly A; Lane, Kimberly; McGrath, Graham; Bazner, Suzane B; Tinsley, Jake; Lennon, Niall J; Henn, Matthew R; Brumme, Zabrina L; Norris, Philip J; Rosenberg, Eric S; Mayer, Kenneth H; Jessen, Heiko; Kosakovsky Pond, Sergei L; Walker, Bruce D; Altfeld, Marcus; Carlson, Jonathan M; Allen, Todd M

    2016-05-01

    Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission. PMID:27163788

  20. Phenotypic heterogeneity in British patients with a founder mutation in the FHL1 gene

    PubMed Central

    Sarkozy, Anna; Windpassinger, Christian; Hudson, Judith; Dougan, Charlotte F; Lecky, Bryan; Hilton-Jones, David; Eagle, Michelle; Charlton, Richard; Barresi, Rita; Lochmüller, Hanns; Bushby, Kate; Straub, Volker

    2011-01-01

    Mutations in the four-and-a-half LIM domain 1 (FHL1) gene, which encodes a 280-amino-acid protein containing four LIM domains and a single zinc-finger domain in the N-terminal region, have been associated with a broad clinical spectrum of X-linked muscle diseases encompassing a variety of different phenotypes. Patients might present with a scapuloperoneal myopathy, a myopathy with postural muscle atrophy and generalized hypertrophy, an Emery–Dreifuss muscular dystrophy, or an early onset myopathy with reducing bodies. It has been proposed that the phenotypic variability is related to the position of the mutation within the FHL1 gene. Here, we report on three British families with a heterogeneous clinical presentation segregating a single FHL1 gene mutation and haplotype, suggesting that this represents a founder mutation. The underlying FHL1 gene mutation was detected by direct sequencing and the founder effect was verified by haplotype analysis of the FHL1 gene locus. A 3-bp insertion mutation (p.Phe127_Thr128insIle) within the second LIM domain of the FHL1 gene was identified in all available affected family members of the three families. Haplotype analysis of the FHL1 region on Xq26 revealed that the families shared a common haplotype. The p.Phe127_Thr128insIle mutation in the FHL1 gene therefore appears to be a British founder mutation and FHL1 gene screening, in particular of exon 6, should therefore be indicated in British patients with a broad phenotypic spectrum of X-linked muscle diseases. PMID:21629301

  1. BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population.

    PubMed

    Nielsen, Henriette Roed; Nilbert, Mef; Petersen, Janne; Ladelund, Steen; Thomassen, Mads; Pedersen, Inge Søkilde; Hansen, Thomas V O; Skytte, Anne-Bine; Borg, Åke; Therkildsen, Christina

    2016-10-01

    Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer.

  2. Tracing European Founder Lineages in the Near Eastern mtDNA Pool

    PubMed Central

    Richards, Martin; Macaulay, Vincent; Hickey, Eileen; Vega, Emilce; Sykes, Bryan; Guida, Valentina; Rengo, Chiara; Sellitto, Daniele; Cruciani, Fulvio; Kivisild, Toomas; Villems, Richard; Thomas, Mark; Rychkov, Serge; Rychkov, Oksana; Rychkov, Yuri; Gölge, Mukaddes; Dimitrov, Dimitar; Hill, Emmeline; Bradley, Dan; Romano, Valentino; Calì, Francesco; Vona, Giuseppe; Demaine, Andrew; Papiha, Surinder; Triantaphyllidis, Costas; Stefanescu, Gheorghe; Hatina, Jiři; Belledi, Michele; Di Rienzo, Anna; Oppenheim, Ariella; Nørby, Søren; Al-Zaheri, Nadia; Santachiara-Benerecetti, Silvana; Scozzari, Rosaria; Torroni, Antonio; Bandelt, Hans-Jürgen

    2000-01-01

    Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2,804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans. PMID:11032788

  3. Andrew Sexton Gray (1826-1907). A founder of Australian ophthalmology: his life and times.

    PubMed

    Lowe, R F

    1985-11-01

    Andrew Sexton Gray was born in Limerick, Ireland, medically trained in Dublin, and was assistant to William Wilde, the distinguished oculist and aurist. He migrated to Victoria in 1859, was surgeon to a railway's construction company, then in 1862 began practice as a surgeon and oculist in Melbourne. In 1863 he founded a charitable eye and ear hospital, and had a very active, long life devoted mostly to ophthalmology. The hospital progressively expanded and became the centre for training for many ophthalmologists, as well as the nucleus for the cohesion of Victorian ophthalmology. History shows Andrew Sexton Gray to have been a founder of Australian ophthalmology. PMID:3914312

  4. Clara Barton: teacher, nurse, Civil War heroine, founder of the American Red Cross.

    PubMed

    Evans, Gerald D

    2003-01-01

    Clara Barton was a nineteenth century woman driven to greatness. She was a teacher, a nurse, a Civil War heroine and founder of the American Red Cross. In order to cut a path into the future we must know where we have been. The story of Clara Barton is about someone who cut that path. It is about courage, overcoming obstacles, never giving up and doing the job that needs doing. What makes it fascinating is the human side, the weaknesses that coloured her life. We can learn from her journey as we develop our own path into the future.

  5. Genetically diverse CC-founder mouse strains replicate the human influenza gene expression signature.

    PubMed

    Elbahesh, Husni; Schughart, Klaus

    2016-05-19

    Influenza A viruses (IAV) are zoonotic pathogens that pose a major threat to human and animal health. Influenza virus disease severity is influenced by viral virulence factors as well as individual differences in host response. We analyzed gene expression changes in the blood of infected mice using a previously defined set of signature genes that was derived from changes in the blood transcriptome of IAV-infected human volunteers. We found that the human signature was reproduced well in the founder strains of the Collaborative Cross (CC) mice, thus demonstrating the relevance and importance of mouse experimental model systems for studying human influenza disease.

  6. Do founder mutations characteristic of some cancer sites also predispose to pancreatic cancer?

    PubMed

    Lener, Marcin R; Scott, Rodney J; Kluźniak, Wojciech; Baszuk, Piotr; Cybulski, Cezary; Wiechowska-Kozłowska, Anna; Huzarski, Tomasz; Byrski, Tomasz; Kładny, Józef; Pietrzak, Sandra; Soluch, Agnieszka; Jakubowska, Anna; Lubiński, Jan

    2016-08-01

    Understanding of the etiology and risk of pancreatic cancer (PaCa) is still poorly understood. This study evaluated the prevalence of 10 Polish founder mutations in four genes among PaCa patients and assessed their possible association with the risk of disease in Poland. In the study 383 PaCa patients and 4,000 control subjects were genotyped for founder mutations in: BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2 + 1G > A, del5395, I157T), NBS1 (657del5) and PALB2 (509_510delGA, 172_175delTTGT). A statistically significant association between the 657del5 mutation and an increased risk of pancreatic cancer was observed for NBS1 gene. The Slavic NBS1 gene mutation (657delACAAA) was detected in 8 of 383 (2.09%) unselected cases compared with 22 of 4,000 (0.55%) controls (OR: 3.80, p = 0.002). The PALB2 509_510delGA and 172_175delTTGT mutations combined were seen in 2 (0.52%) unselected cases of PaCa and in 8 (0.20%) of 4,000 controls (OR: 2.61, p = 0.49). For BRCA1, the three mutations combined were detected in 4 of 383 (1.04%) PaCa patients and in 17 of 4,000 (0.42%) controls (OR: 2.46, p = 0.20). CHEK2 mutations were not associated with the risk of pancreatic cancer (OR: 1.11, p = 0.72). The founder mutation in NBS1 (657del5) was associated with an increased risk of PaCa in heterozygous carriers, indicating that this mutation appears to predispose to cancer of the pancreas. By identifying pancreatic cancer risk groups, founder mutation testing in Poland should be considered for people at risk for PaCa. PMID:27038244

  7. Rapid and efficient analysis of gene function using CRISPR-Cas9 in Xenopus tropicalis founders.

    PubMed

    Shigeta, Mitsuki; Sakane, Yuto; Iida, Midori; Suzuki, Miyuki; Kashiwagi, Keiko; Kashiwagi, Akihiko; Fujii, Satoshi; Yamamoto, Takashi; Suzuki, Ken-Ichi T

    2016-07-01

    Recent advances in genome editing using programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system, have facilitated reverse genetics in Xenopus tropicalis. To establish a practical workflow for analyzing genes of interest using CRISPR-Cas9, we examined various experimental procedures and conditions. We first compared the efficiency of gene disruption between Cas9 protein and mRNA injection by analyzing genotype and phenotype frequency, and toxicity. Injection of X. tropicalis embryos with Cas9 mRNA resulted in high gene-disrupting efficiency comparable with that produced by Cas9 protein injection. To exactly evaluate the somatic mutation rates of on-target sites, amplicon sequencing and restriction fragment length polymorphism analysis using a restriction enzyme or recombinant Cas9 were performed. Mutation rates of two target genes (slc45a2 and ltk) required for pigmentation were estimated to be over 90% by both methods in animals exhibiting severe phenotypes, suggesting that targeted somatic mutations were biallelically introduced in almost all somatic cells of founder animals. Using a heteroduplex mobility assay, we also showed that off-target mutations were induced at a low rate. Based on our results, we propose a CRISPR-Cas9-mediated gene disruption workflow for a rapid and efficient analysis of gene function using X. tropicalis founders.

  8. Population genetics reveals origin and number of founders in a biological invasion.

    PubMed

    Ficetola, Gentile Francesco; Bonin, Aurelie; Miaud, Claude

    2008-02-01

    Propagule pressure is considered the main determinant of success of biological invasions: when a large number of individuals are introduced into an area, the species is more likely to establish and become invasive. Nevertheless, precise data on propagule pressure exist only for a small sample of invasive species, usually voluntarily introduced. We studied the invasion of the American bullfrog, Rana catesbeiana, into Europe, a species that is considered a major cause of decline for native amphibians. For this major invader with scarce historical data, we used population genetics data (a partial sequence of the mitochondrial cytochrome b gene) to infer the invasion history and to estimate the number of founders of non-native populations. Based on differences between populations, at least six independent introductions from the native range occurred in Europe, followed by secondary translocations. Genetic diversity was strongly reduced in non-native populations, indicating a very strong bottleneck during colonization. We used simulations to estimate the precise number of founders and found that most non-native populations derive from less than six females. This capability of invasion from a very small number of propagules challenges usual management strategies; species with such ability should be identified at an early stage of introduction. PMID:18194168

  9. Serial founder effects and genetic differentiation during worldwide range expansion of monarch butterflies

    PubMed Central

    Pierce, Amanda A.; Zalucki, Myron P.; Bangura, Marie; Udawatta, Milan; Kronforst, Marcus R.; Altizer, Sonia; Haeger, Juan Fernández; de Roode, Jacobus C.

    2014-01-01

    Range expansions can result in founder effects, increasing genetic differentiation between expanding populations and reducing genetic diversity along the expansion front. However, few studies have addressed these effects in long-distance migratory species, for which high dispersal ability might counter the effects of genetic drift. Monarchs (Danaus plexippus) are best known for undertaking a long-distance annual migration in North America, but have also dispersed around the world to form populations that do not migrate or travel only short distances. Here, we used microsatellite markers to assess genetic differentiation among 18 monarch populations and to determine worldwide colonization routes. Our results indicate that North American monarch populations connected by land show limited differentiation, probably because of the monarch's ability to migrate long distances. Conversely, we found high genetic differentiation between populations separated by large bodies of water. Moreover, we show evidence for serial founder effects across the Pacific, suggesting stepwise dispersal from a North American origin. These findings demonstrate that genetic drift played a major role in shaping allele frequencies and created genetic differentiation among newly formed populations. Thus, range expansion can give rise to genetic differentiation and declines in genetic diversity, even in highly mobile species. PMID:25377462

  10. Role of founder cell deficit and delayed neuronogenesis in microencephaly of the trisomy 16 mouse

    NASA Technical Reports Server (NTRS)

    Haydar, T. F.; Nowakowski, R. S.; Yarowsky, P. J.; Krueger, B. K.

    2000-01-01

    Development of the neocortex of the trisomy 16 (Ts16) mouse, an animal model of Down syndrome (DS), is characterized by a transient delay in the radial expansion of the cortical wall and a persistent reduction in cortical volume. Here we show that at each cell cycle during neuronogenesis, a smaller proportion of Ts16 progenitors exit the cell cycle than do control, euploid progenitors. In addition, the cell cycle duration was found to be longer in Ts16 than in euploid progenitors, the Ts16 growth fraction was reduced, and an increase in apoptosis was observed in both proliferative and postmitotic zones of the developing Ts16 neocortical wall. Incorporation of these changes into a model of neuronogenesis indicates that they are sufficient to account for the observed delay in radial expansion. In addition, the number of neocortical founder cells, i.e., precursors present just before neuronogenesis begins, is reduced by 26% in Ts16 mice, leading to a reduction in overall cortical size at the end of Ts16 neuronogenesis. Thus, altered proliferative characteristics during Ts16 neuronogenesis result in a delay in the generation of neocortical neurons, whereas the founder cell deficit leads to a proportional reduction in the overall number of neurons. Such prenatal perturbations in either the timing of neuron generation or the final number of neurons produced may lead to significant neocortical abnormalities such as those found in DS.

  11. PRIMAL: Fast and Accurate Pedigree-based Imputation from Sequence Data in a Founder Population

    PubMed Central

    Livne, Oren E.; Han, Lide; Alkorta-Aranburu, Gorka; Wentworth-Sheilds, William; Abney, Mark; Ober, Carole; Nicolae, Dan L.

    2015-01-01

    Founder populations and large pedigrees offer many well-known advantages for genetic mapping studies, including cost-efficient study designs. Here, we describe PRIMAL (PedigRee IMputation ALgorithm), a fast and accurate pedigree-based phasing and imputation algorithm for founder populations. PRIMAL incorporates both existing and original ideas, such as a novel indexing strategy of Identity-By-Descent (IBD) segments based on clique graphs. We were able to impute the genomes of 1,317 South Dakota Hutterites, who had genome-wide genotypes for ~300,000 common single nucleotide variants (SNVs), from 98 whole genome sequences. Using a combination of pedigree-based and LD-based imputation, we were able to assign 87% of genotypes with >99% accuracy over the full range of allele frequencies. Using the IBD cliques we were also able to infer the parental origin of 83% of alleles, and genotypes of deceased recent ancestors for whom no genotype information was available. This imputed data set will enable us to better study the relative contribution of rare and common variants on human phenotypes, as well as parental origin effect of disease risk alleles in >1,000 individuals at minimal cost. PMID:25735005

  12. Can a linguistic serial founder effect originating in Africa explain the worldwide phonemic cline?

    PubMed Central

    2016-01-01

    It has been proposed that a serial founder effect could have caused the present observed pattern of global phonemic diversity. Here we present a model that simulates the human range expansion out of Africa and the subsequent spatial linguistic dynamics until today. It does not assume copying errors, Darwinian competition, reduced contrastive possibilities or any other specific linguistic mechanism. We show that the decrease of linguistic diversity with distance (from the presumed origin of the expansion) arises under three assumptions, previously introduced by other authors: (i) an accumulation rate for phonemes; (ii) small phonemic inventories for the languages spoken before the out-of-Africa dispersal; (iii) an increase in the phonemic accumulation rate with the number of speakers per unit area. Numerical simulations show that the predictions of the model agree with the observed decrease of linguistic diversity with increasing distance from the most likely origin of the out-of-Africa dispersal. Thus, the proposal that a serial founder effect could have caused the present observed pattern of global phonemic diversity is viable, if three strong assumptions are satisfied. PMID:27122180

  13. Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families.

    PubMed Central

    Tonin, P N; Mes-Masson, A M; Futreal, P A; Morgan, K; Mahon, M; Foulkes, W D; Cole, D E; Provencher, D; Ghadirian, P; Narod, S A

    1998-01-01

    We have identified four mutations in each of the breast cancer-susceptibility genes, BRCA1 and BRCA2, in French Canadian breast cancer and breast/ovarian cancer families from Quebec. To identify founder effects, we examined independently ascertained French Canadian cancer families for the distribution of these eight mutations. Mutations were found in 41 of 97 families. Six of eight mutations were observed at least twice. The BRCA1 C4446T mutation was the most common mutation found, followed by the BRCA2 8765delAG mutation. Together, these mutations were found in 28 of 41 families identified to have a mutation. The odds of detection of any of the four BRCA1 mutations was 18.7x greater if one or more cases of ovarian cancer were also present in the family. The odds of detection of any of the four BRCA2 mutations was 5.3x greater if there were at least five cases of breast cancer in the family. Interestingly, the presence of a breast cancer case <36 years of age was strongly predictive of the presence of any of the eight mutations screened. Carriers of the same mutation, from different families, shared similar haplotypes, indicating that the mutant alleles were likely to be identical by descent for a mutation in the founder population. The identification of common BRCA1 and BRCA2 mutations will facilitate carrier detection in French Canadian breast cancer and breast/ovarian cancer families. PMID:9792861

  14. Can a linguistic serial founder effect originating in Africa explain the worldwide phonemic cline?

    PubMed

    Fort, Joaquim; Pérez-Losada, Joaquim

    2016-04-01

    It has been proposed that a serial founder effect could have caused the present observed pattern of global phonemic diversity. Here we present a model that simulates the human range expansion out of Africa and the subsequent spatial linguistic dynamics until today. It does not assume copying errors, Darwinian competition, reduced contrastive possibilities or any other specific linguistic mechanism. We show that the decrease of linguistic diversity with distance (from the presumed origin of the expansion) arises under three assumptions, previously introduced by other authors: (i) an accumulation rate for phonemes; (ii) small phonemic inventories for the languages spoken before the out-of-Africa dispersal; (iii) an increase in the phonemic accumulation rate with the number of speakers per unit area. Numerical simulations show that the predictions of the model agree with the observed decrease of linguistic diversity with increasing distance from the most likely origin of the out-of-Africa dispersal. Thus, the proposal that a serial founder effect could have caused the present observed pattern of global phonemic diversity is viable, if three strong assumptions are satisfied. PMID:27122180

  15. Origin of sexual isolation in Drosophila ananassae due to founder effects.

    PubMed

    Nanda, Punita; Singh, Bashisth N

    2011-06-01

    The origin of sexual isolation is the central event in the evolution of biological species and plays a key role in maintaining biological diversity. Three mass culture stocks of D. ananassae originating from different geographic localities showing no isolation with each other were subjected to different degrees of bottlenecks i.e. one pair, five pairs and ten pairs. These drift lines were passed through flush-crash cycle at every generation with same initial number of founders, and maintained for twenty-seven generations and then the pattern of matings was tested among these nine drift lines involving 36 crosses in total. In 23 of 36 crosses, the difference between homogamic and heterogamic matings was significant and isolation indices were significantly more than zero in one direction only providing evidence for asymmetrical sexual isolation. Further, when Bonferroni test for pair-wise analysis was employed, significant differences between homogamic and heterogamic matings were found in 25 crosses. These findings provide evidence for origin of sexual isolation by founder effects in D. ananassae.

  16. Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia.

    PubMed

    Ben Brick, Ahlem Sabrine; Laroussi, Nadia; Mesrati, Hela; Kefi, Rym; Bchetnia, Mbarka; Lasram, Khaled; Ben Halim, Nizar; Romdhane, Lilia; Ouragini, Houyem; Marrakchi, Salaheddine; Boubaker, Mohamed Samir; Meddeb Cherif, Mounira; Castiglia, Daniele; Hovnanian, Alain; Abdelhak, Sonia; Turki, Hamida

    2014-05-01

    Dystrophic epidermolysis bullosa (DEB) is a group of heritable bullous skin disorders caused by mutations in the COL7A1 gene. One of the most severe forms of DEB is the severe generalized [recessive dystrophic epidermolysis bullosa (RDEB-SG)] subtype, which is inherited in an autosomal recessive manner. This subtype is most often due to COL7A1 mutations resulting in a premature termination codon on both alleles. We report here, the molecular investigation of 15 patients belonging to 14 nuclear families from the city of Sfax in Southern Tunisia, with clinical features of RDEB-SG complicated by squamous cell carcinoma in 3 patients. We identified two novel mutations, p.Val769LeufsX1 and p.Ala2297SerfsX91, in addition to one previously reported mutation (p.Arg2063Trp). The p.Val769LeufsX1 mutation was shared by 11 families and haplotype analysis indicated that it is a founder mutation. The p.Ala2297SerfsX91 mutation was a private mutation found in only one family. Together with the previously described recurrent mutations in Tunisia, screening for the founder p.Val769LeufsX1 mutation should provide a rapid molecular diagnosis tool for mutation screening in RDEB patients from Southern Tunisia and possibly from other Mediterranean populations sharing the same genetic background.

  17. Founder control and coexistence in a simple model of asymmetric competition for light.

    PubMed

    Perry, Laura G; Neuhauser, Claudia; Galatowitsch, Susan M

    2003-06-21

    Size asymmetry in plant light acquisition complicates predictions of competitive outcomes in light-limited communities. We present a mathematically tractable model of asymmetric competition for light and discuss its implications for predicting outcomes of competition during establishment in two-, three-, and many-species communities. In contrast to the resource-reduction model of symmetric competition for a single resource, the model we present predicts that outcomes of asymmetric competition for light will sometimes depend on the timing of establishment and the consequent hierarchy among species in canopy position. Competitive outcomes in the model depend on the minimum light requirements (L(c)) and self-shading of species lower in the canopy compared to the light available (L(out)(*)) beneath species higher in the canopy. Succession progresses towards species with decreasing values for L(c), but arrested successions occur when initial dominants have relatively high values for L(c) but low values for L(out)(*), leading to founder control. A theoretically limitless number of species may coexist in competition for light when dominance is founder controlled. These model predictions have implications for an array of applied ecological questions, including methods to control invasive species in light-limited restored ecosystems.

  18. Signatures of seaway closures and founder dispersal in the phylogeny of a circumglobally distributed seahorse lineage

    PubMed Central

    Teske, Peter R; Hamilton, Healy; Matthee, Conrad A; Barker, Nigel P

    2007-01-01

    Background The importance of vicariance events on the establishment of phylogeographic patterns in the marine environment is well documented, and generally accepted as an important cause of cladogenesis. Founder dispersal (i.e. long-distance dispersal followed by founder effect speciation) is also frequently invoked as a cause of genetic divergence among lineages, but its role has long been challenged by vicariance biogeographers. Founder dispersal is likely to be common in species that colonize remote habitats by means of rafting (e.g. seahorses), as long-distance dispersal events are likely to be rare and subsequent additional recruitment from the source habitat is unlikely. In the present study, the relative importance of vicariance and founder dispersal as causes of cladogenesis in a circumglobally distributed seahorse lineage was investigated using molecular dating. A phylogeny was reconstructed using sequence data from mitochondrial and nuclear markers, and the well-documented closure of the Central American seaway was used as a primary calibration point to test whether other bifurcations in the phylogeny could also have been the result of vicariance events. The feasibility of three other vicariance events was explored: a) the closure of the Indonesian Seaway, resulting in sister lineages associated with the Indian Ocean and West Pacific, respectively; b) the closure of the Tethyan Seaway, resulting in sister lineages associated with the Indo-Pacific and Atlantic Ocean, respectively, and c) continental break-up during the Mesozoic followed by spreading of the Atlantic Ocean, resulting in pairs of lineages with amphi-Atlantic distribution patterns. Results Comparisons of pairwise genetic distances among the seahorse species hypothesized to have diverged as a result of the closure of the Central American Seaway with those of published teleost sequences having the same distribution patterns show that the seahorses were among the last to diverge. This suggests

  19. Strong Amerind/White Sex Bias and a Possible Sephardic Contribution among the Founders of a Population in Northwest Colombia

    PubMed Central

    Carvajal-Carmona, Luis G.; Soto, Iván D.; Pineda, Nicolás; Ortíz-Barrientos, Daniel; Duque, Constanza; Ospina-Duque, Jorge; McCarthy, Mark; Montoya, Patricia; Alvarez, Victor M.; Bedoya, Gabriel; Ruiz-Linares, Andrés

    2000-01-01

    Historical and genetic evidences suggest that the recently founded population of Antioquia (Colombia) is potentially useful for the genetic mapping of complex traits. This population was established in the 16th–17th centuries through the admixture of Amerinds, Europeans, and Africans and grew in relative isolation until the late 19th century. To examine the origin of the founders of Antioquia, we typed 11 markers on the nonrecombining portion of the Y chromosome and four markers on mtDNA in a sample of individuals with confirmed Antioquian ancestry. The polymorphisms on the Y chromosome (five biallelic markers and six microsatellites) allow an approximation to the origin of founder men, and those on mtDNA identify the four major founder Native American lineages. These data indicate that ∼94% of the Y chromosomes are European, 5% are African, and 1% are Amerind. Y-chromosome data are consistent with an origin of founders predominantly in southern Spain but also suggest that a fraction came from northern Iberia and that some possibly had a Sephardic origin. In stark contrast with the Y-chromosome, ∼90% of the mtDNA gene pool of Antioquia is Amerind, with the frequency of the four Amerind founder lineages being closest to Native Americans currently living in the area. These results indicate a highly asymmetric pattern of mating in early Antioquia, involving mostly immigrant men and local native women. The discordance of our data with blood-group estimates of admixture suggests that the number of founder men was larger than that of women. PMID:11032790

  20. Clinal patterns of human Y chromosomal diversity in continental Italy and Greece are dominated by drift and founder effects.

    PubMed

    Di Giacomo, F; Luca, F; Anagnou, N; Ciavarella, G; Corbo, R M; Cresta, M; Cucci, F; Di Stasi, L; Agostiano, V; Giparaki, M; Loutradis, A; Mammi', C; Michalodimitrakis, E N; Papola, F; Pedicini, G; Plata, E; Terrenato, L; Tofanelli, S; Malaspina, P; Novelletto, A

    2003-09-01

    We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 30 population samples from closely spaced locations in Italy and Greece for 9 haplogroups and their internal microsatellite variation. We confirm a significant difference in the composition of the Y chromosomal gene pools of the two countries. However, within each country, heterogeneity is not organized along the lines of clinal variation deduced from studies on larger spatial scales. Microsatellite data indicate that local increases of haplogroup frequencies can be often explained by a limited number of founders. We conclude that local founder or drift effects are the main determinants in shaping the microgeographic Y chromosomal diversity.

  1. Associations of High-Grade Prostate Cancer with BRCA1 and BRCA2 Founder Mutations

    PubMed Central

    Agalliu, Ilir; Gern, Robert; Leanza, Suzanne; Burk, Robert D.

    2013-01-01

    Purpose Protein-truncating mutations in BRCA1 and in particular BRCA2 genes have been associated with prostate cancer. However, there is still uncertainty about the magnitude of association particularly with Gleason score, and family history of prostate, breast, and ovary cancers. Experimental Design To further examine associations between three founder mutations located in BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) genes and prostate cancer, we conducted a study of 979 prostate cancer cases and 1,251 controls among Ashkenazi Jewish men. Detailed information was obtained on prostate cancer pathology, age at diagnosis, and family history of all cancers. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression models. Results Prostate cancer risk was increased (OR, 1.9; 95% CI 0.9-4.1) for BRCA2 mutation carriers but not for BRCA1 mutation carriers. BRCA2 mutation carriers had an OR of 3.2 (95% CI, 1.4-7.3) for Gleason score of 7 to 10, but no association was observed for Gleason score of <7. Carriers of BRCA1-185delAG mutation also had an OR of 3.5 (95% CI, 1.2-10.3) for Gleason score of ≥7 tumors; however, the association of either BRCA1-185delAG or 5382insC mutation was not statistically significant. Associations between founder mutations and prostate cancer were stronger in men with no first-degree family history of breast and/or ovarian cancers but were unaffected by family history of prostate cancer. Conclusion These results indicate that the BRCA2 founder mutation confers a 3-fold elevated risk of high-grade prostate cancer. Although BRCA1 mutations were not associated with prostate cancer, the BRCA1-185delAG was associated with high Gleason score tumors. These findings should be carefully considered in genetic counseling and/or evaluating therapeutic options. PMID:19188187

  2. PedHunter 2.0 and its usage to characterize the founder structure of the Old Order Amish of Lancaster County

    PubMed Central

    2010-01-01

    Background Because they are a closed founder population, the Old Order Amish (OOA) of Lancaster County have been the subject of many medical genetics studies. We constructed four versions of Anabaptist Genealogy Database (AGDB) using three sources of genealogies and multiple updates. In addition, we developed PedHunter, a suite of query software that can solve pedigree-related problems automatically and systematically. Methods We report on how we have used new features in PedHunter to quantify the number and expected genetic contribution of founders to the OOA. The queries and utility of PedHunter programs are illustrated by examples using AGDB in this paper. For example, we calculated the number of founders expected to be contributing genetic material to the present-day living OOA and estimated the mean relative founder representation for each founder. New features in PedHunter also include pedigree trimming and pedigree renumbering, which should prove useful for studying large pedigrees. Results With PedHunter version 2.0 querying AGDB version 4.0, we identified 34,160 presumed living OOA individuals and connected them into a 14-generation pedigree descending from 554 founders (332 females and 222 males) after trimming. From the analysis of cumulative mean relative founder representation, 128 founders (78 females and 50 males) accounted for over 95% of the mean relative founder contribution among living OOA descendants. Discussion/Conclusions The OOA are a closed founder population in which a modest number of founders account for the genetic variation present in the current OOA population. Improvements to the PedHunter software will be useful in future studies of both the OOA and other populations with large and computerized genealogies. PMID:20433770

  3. A Common Founder Mutation in the EDA-A1 Gene in X-Linked Hypodontia

    PubMed Central

    Kurban, Mazen; Michailidis, Eleni; Wajid, Muhammad; Shimomura, Yutaka; Christiano, Angela M.

    2010-01-01

    Background X-linked recessive hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is a rare genodermatosis characterized clinically by developmental abnormalities affecting the teeth, hair and sweat glands. Mutations in the EDA-A1 gene have been associated with XLHED. Recently, mutations in the EDA-A1 gene have also been implicated in isolated X-linked recessive hypodontia (XLRH; OMIM 313500). Methods We analyzed the DNA from members of 3 unrelated Pakistani families with XLRH for mutations in the EDA-A1 gene through direct sequencing and performed haplotype analysis. Results We identified a common missense mutation in both families designated c.1091T→C (p.M364T). Haplotype analysis revealed that this is a founder mutation in the 3 families. Conclusion XLHED is a syndrome with variable clinical presentations that contain a spectrum of findings, including hypodontia. We suggest that XLRH should be grouped under XLHED as both share several phenotypic and genotypic similarities. PMID:20628232

  4. Eduard Strasburger (1844-1912): founder of modern plant cell biology.

    PubMed

    Volkmann, Dieter; Baluška, František; Menzel, Diedrik

    2012-10-01

    Eduard Strasburger, director of the Botany Institute and the Botanical Garden at the University of Bonn from 1881 to 1912, was one of the most admirable scientists in the field of plant biology, not just as the founder of modern plant cell biology but in addition as an excellent teacher who strongly believed in "education through science." He contributed to plant cell biology by discovering the discrete stages of karyokinesis and cytokinesis in algae and higher plants, describing cytoplasmic streaming in different systems, and reporting on the growth of the pollen tube into the embryo sac and guidance of the tube by synergides. Strasburger raised many problems which are hot spots in recent plant cell biology, e.g., structure and function of the plasmodesmata in relation to phloem loading (Strasburger cells) and signaling, mechanisms of cell plate formation, vesicle trafficking as a basis for most important developmental processes, and signaling related to fertilization.

  5. Evidence for a "Founder Effect" among HIV-infected injection drug users (IDUs) in Pakistan

    PubMed Central

    2010-01-01

    Background We have previously reported a HIV-1 subtype A infection in a community of injection drug users (IDUs) in Karachi, Pakistan. We now show that this infection among the IDUs may have originated from a single source. Methods Phylogenetic analysis was performed of partial gag sequences, generated using PCR, from 26 HIV-positive IDU samples. Results Our results showed formation of a tight monophyletic group with an intra-sequence identity of < 98% indicating a "founder effect". Our data indicate that the HIV-1 epidemic in this community of IDUs may have been transmitted by an HIV positive overseas contract worker who admitted to having contact with commercial sex workers during stay abroad. Conclusion Specific measures need to implemented to control transmission of HIV infection in Pakistan through infected migrant workers. PMID:20064274

  6. John D. Rockefeller 3rd, statesman and founder of the Population Council.

    PubMed

    Dunlop, J

    2000-01-01

    This article presents a profile of John D. Rockefeller 3rd, statesman and founder of the Population Council. It is noted that Rockefeller took a broad view of population control as a means to address poverty and economic development rather than as an end in itself. In 1952 he initiated the convocation of the Conference on Population Problems held in Williamsburg, Virginia. The discussion focused on food supply, industrial development, depletion of natural resources, and political instability resulting from unchecked population growth. In 1967, Rockefeller initiated, lobbied for, and finally achieved a World Leaders' Statement signed by 30 heads of state including US President Lyndon Johnson. The document drew attention to population growth as a world problem and engendered political support for family planning as a solution. After 3 years the Commission on Population Growth and the American Future was established, and Rockefeller was made its chairman. Several issues were debated, including more safer fertility control and the legalization of abortion.

  7. Linkage-disequilibrium mapping of disease genes by reconstruction of ancestral haplotypes in founder populations.

    PubMed Central

    Service, S K; Lang, D W; Freimer, N B; Sandkuijl, L A

    1999-01-01

    Linkage disequilibrium (LD) mapping may be a powerful means for genome screening to identify susceptibility loci for common diseases. A new statistical approach for detection of LD around a disease gene is presented here. This method compares the distribution of haplotypes in affected individuals versus that expected for individuals descended from a common ancestor who carried a mutation of the disease gene. Simulations demonstrate that this method, which we term "ancestral haplotype reconstruction" (AHR), should be powerful for genome screening of phenotypes characterized by a high degree of etiologic heterogeneity, even with currently available marker maps. AHR is best suited to application in isolated populations where affected individuals are relatively recently descended (< approximately 25 generations) from a common disease mutation-bearing founder. PMID:10330361

  8. Distribution and medical impact of loss-of-function variants in the Finnish founder population.

    PubMed

    Lim, Elaine T; Würtz, Peter; Havulinna, Aki S; Palta, Priit; Tukiainen, Taru; Rehnström, Karola; Esko, Tõnu; Mägi, Reedik; Inouye, Michael; Lappalainen, Tuuli; Chan, Yingleong; Salem, Rany M; Lek, Monkol; Flannick, Jason; Sim, Xueling; Manning, Alisa; Ladenvall, Claes; Bumpstead, Suzannah; Hämäläinen, Eija; Aalto, Kristiina; Maksimow, Mikael; Salmi, Marko; Blankenberg, Stefan; Ardissino, Diego; Shah, Svati; Horne, Benjamin; McPherson, Ruth; Hovingh, Gerald K; Reilly, Muredach P; Watkins, Hugh; Goel, Anuj; Farrall, Martin; Girelli, Domenico; Reiner, Alex P; Stitziel, Nathan O; Kathiresan, Sekar; Gabriel, Stacey; Barrett, Jeffrey C; Lehtimäki, Terho; Laakso, Markku; Groop, Leif; Kaprio, Jaakko; Perola, Markus; McCarthy, Mark I; Boehnke, Michael; Altshuler, David M; Lindgren, Cecilia M; Hirschhorn, Joel N; Metspalu, Andres; Freimer, Nelson B; Zeller, Tanja; Jalkanen, Sirpa; Koskinen, Seppo; Raitakari, Olli; Durbin, Richard; MacArthur, Daniel G; Salomaa, Veikko; Ripatti, Samuli; Daly, Mark J; Palotie, Aarno

    2014-07-01

    Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10⁻⁸) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10⁻¹¹⁷). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10⁻⁴), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.

  9. Novel origins of lineage founder cells in the direct-developing sea urchin Heliocidaris erythrogramma.

    PubMed

    Wray, G A; Raff, R A

    1990-09-01

    The lineage and fate of each blastomere in the 32-cell embryo of the direct-developing sea urchin Heliocidaris erythrogramma have been traced by microinjection of tetramethylrhodamine-dextran. The results reveal substantive evolutionary modifications of the ancestral cell lineage pattern of indirect sea urchin development. Significant among these modifications are changes in the time and order of cell lineage segregation: vegetal ectodermal founder cells consistently arise earlier than during indirect development, while internal founder cells generally segregate later and in a different sequence. Modifications have also arisen in proportions of the embryo fated to become various cell types and larval structures. Ectodermal fates, particularly vestibular ectoderm, comprise a greater proportion of the total cellular volume in H. erythrogramma. Among internal cell types, coelom consumes more and endoderm less of the remaining cellular volume than during indirect sea urchin development. Evolutionary modifications are also apparent in the positional origin of larval cell types and structures in H. erythrogramma. These include an apparent tilt in the axis of prospective cell fate relative to the animal-vegetal axis as defined by cleavage planes. Together these evolutionary changes in the cell lineage of H. erythrogramma produce an accelerated loss of dorsoventral symmetry in cell fate relative to indirect development. The extent and diversity of rearrangements in its cell lineage indicate that the non-feeding larva of H. erythrogramma is a highly modified, novel form rather than a degenerate pluteus larva. These same modifications underscore the evolutionarily flexible relationship between cell lineage, gene expression, and larval morphology in sea urchin development.

  10. Distribution and medical impact of loss-of-function variants in the Finnish founder population.

    PubMed

    Lim, Elaine T; Würtz, Peter; Havulinna, Aki S; Palta, Priit; Tukiainen, Taru; Rehnström, Karola; Esko, Tõnu; Mägi, Reedik; Inouye, Michael; Lappalainen, Tuuli; Chan, Yingleong; Salem, Rany M; Lek, Monkol; Flannick, Jason; Sim, Xueling; Manning, Alisa; Ladenvall, Claes; Bumpstead, Suzannah; Hämäläinen, Eija; Aalto, Kristiina; Maksimow, Mikael; Salmi, Marko; Blankenberg, Stefan; Ardissino, Diego; Shah, Svati; Horne, Benjamin; McPherson, Ruth; Hovingh, Gerald K; Reilly, Muredach P; Watkins, Hugh; Goel, Anuj; Farrall, Martin; Girelli, Domenico; Reiner, Alex P; Stitziel, Nathan O; Kathiresan, Sekar; Gabriel, Stacey; Barrett, Jeffrey C; Lehtimäki, Terho; Laakso, Markku; Groop, Leif; Kaprio, Jaakko; Perola, Markus; McCarthy, Mark I; Boehnke, Michael; Altshuler, David M; Lindgren, Cecilia M; Hirschhorn, Joel N; Metspalu, Andres; Freimer, Nelson B; Zeller, Tanja; Jalkanen, Sirpa; Koskinen, Seppo; Raitakari, Olli; Durbin, Richard; MacArthur, Daniel G; Salomaa, Veikko; Ripatti, Samuli; Daly, Mark J; Palotie, Aarno

    2014-07-01

    Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10⁻⁸) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10⁻¹¹⁷). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10⁻⁴), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers. PMID

  11. Local mitochondrial DNA haplotype databases needed for domestic dog populations that have experienced founder effect.

    PubMed

    Spadaro, Amanda; Ream, Kelsey; Braham, Caitlyn; Webb, Kristen M

    2015-03-01

    Biological material from pets is often collected as evidence from crime scenes. Due to sample type and quality, mitochondrial DNA (mtDNA) is frequently evaluated to identify the potential contributor. MtDNA has a lower discriminatory power than nuclear DNA with multiple individuals in a population potentially carrying the same mtDNA sequence, or haplotype. The frequency distribution of mtDNA haplotypes in a population must be known in order to determine the evidentiary value of a match between crime scene evidence and the potential contributor of the biological material. This is especially important in geographic areas that include remote and/or isolated populations where founder effect may have lead to a decrease in genetic diversity and a non-random distribution of haplotypes relative to the population at large. Here we compared the haplotype diversity in dogs from the noncontiguous states of Alaska and Hawaii relative to the contiguous United States (US). We report a greater proportion of dogs carrying an A haplotype in Alaska relative to any other US population. Significant variation in the distribution of haplotype frequencies was discovered when comparing the haplotype diversity of dogs in Hawaii to that of the continental US. Each of these regions exhibits reduced genetic diversity relative to the contiguous US, likely due to founder effect. We recommend that specific databases be created to accurately represent the mitochondrial haplotype diversity in these remote areas. Furthermore, our work demonstrates the importance of local surveys for populations that may have experienced found effect. PMID:25612881

  12. The split of the Arara population: comparison of genetic drift and founder effect.

    PubMed

    Ribeiro-dos-Santos, A K; Guerreiro, J F; Santos, S E; Zago, M A

    2001-01-01

    The total genetic diversity of the Amerindian population is as high as that observed for other continental human populations because a large contribution from variation among tribes makes up for the low variation within tribes. This is attributed mainly to genetic drift acting on small isolated populations. However, a small founder population with a low genetic diversity is another factor that may contribute to the low intratribal diversity. Small founder populations seem to be a frequent event in the formation of new tribes among the Amerindians, but this event is usually not well recorded. In this paper, we analyze the genetic diversity of the Arara of Laranjal village and the Arara of Iriri village, with respect to seven tandem repeat autosomic segments (D1S80, ApoB, D4S43, vW1, vW2, F13A1 and D12S67), two Y-chromosome-specific polymorphisms (DYS19 and DYS199), and mitochondrial DNA (mtDNA) markers (restriction fragment length polymorphisms and sequencing of a segment of the D loop region). The occurrence of a single Y chromosome and mtDNA haplotype, and only 1-4 alleles of the autosomic loci investigated, corroborates historic and demographic records that the Arara of Iriri were founded by a single couple of siblings who came from the Arara of Laranjal, the largest group. Notwithstanding this fact, the genetic distance and the molecular variance between the two Arara villages were greater than those observed between them and other Amazonian tribes, suggesting that the microevolutionary process among Brazilian Amerindians may be misinterpreted if historic demographic data are not considered.

  13. Search for a founder mutation in idiopathic focal dystonia from Northern Germany.

    PubMed Central

    Klein, C; Ozelius, L J; Hagenah, J; Breakefield, X O; Risch, N J; Vieregge, P

    1998-01-01

    Both the discovery of the DYT1 gene on chromosome 9q34 in autosomal dominant early-onset torsion dystonia and the detection of linkage for one form of adult-onset focal dystonia to chromosome 18p (DYT7) in a family from northern Germany provide the opportunity to further investigate genetic factors in the focal dystonias. Additionally, reports of linkage disequilibrium between several chromosome 18 markers and focal dystonia, both in sporadic patients from northern Germany and in members of affected families from central Europe suggest the existence of a founder mutation underlying focal dystonia in this population. To evaluate the role of these loci in focal dystonia, we tested 85 patients from northern Germany who had primary focal dystonia, both for the GAG deletion in the DYT1 gene on chromosome 9q34 and for linkage disequilibrium at the chromosome 18p markers D18S1105, D18S1098, D18S481, and D18S54. None of these patients had the GAG deletion in the DYT1 gene. Furthermore, Hardy-Weinberg analysis of markers on 18p in our patient population and in 85 control subjects from the same region did not support linkage disequilibrium. Taken together, these results suggest that most cases of focal dystonia in patients of northern German or central European origin are due neither to the GAG deletion in DYT1 nor to a proposed founder mutation on chromosome 18p but must be caused by other genetic or environmental factors. PMID:9837831

  14. Compositional assessments of key maize populations: B73 hybrids of the nested association mapping founder lines and diverse landrace inbred lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study provides an assessment of compositional diversity in maize B73 hybrids derived from both the nested association mapping (NAM) founder lines and from a geographically diverse collection of landrace accessions from North and South America. The NAM founders represent a key population...

  15. TGfU--Would You Know It if You Saw It? Benchmarks from the Tacit Knowledge of the Founders

    ERIC Educational Resources Information Center

    Butler, Joy

    2014-01-01

    This paper explores the tacit expert knowledge and understanding about games curriculum and pedagogy of three men, Len Almond, David Bunker, and Rod Thorpe, credited as the founders of the Teaching Games for Understanding (TGfU) model. The model emerged from teacher practice in the late 1970s and was little theorized at the time, apart from a…

  16. Torsten Husén--A Co-Founder and Chairman of IEA from 1962 to 1978

    ERIC Educational Resources Information Center

    Genova, Teodora

    2015-01-01

    This paper reviews the work and contribution of one of the most influential comparativists in education--Torsten Husén in the period when he was a co-founder and chairman of the International Association for the Evaluation of Educational Achievement (IEA) in the 60 and 70 decades of the 20th century. At that particular time, the first major…

  17. Remembering Nancy. 25 Members of the Montessori Community Share Their Reflections on the Death of the AMS Founder.

    ERIC Educational Resources Information Center

    Turner, Joy; And Others

    1995-01-01

    Twenty-five members of the Montessori community share their memories of Dr. Nancy McCormick Rambusch, charismatic founder of the American Montessori movement, early childhood professional, and innovative educator, who died of pancreatic cancer on October 27, 1994. Rambusch's work of 40 years now flowers as an institutionalized educational program…

  18. Hereditary Sensory Neuropathy Type I: Haplotype Analysis Shows Founders in Southern England and Europe

    PubMed Central

    Nicholson, G. A.; Dawkins, J. L.; Blair, I. P.; Auer-Grumbach, M.; Brahmbhatt, S. B.; Hulme, D. J.

    2001-01-01

    Hereditary sensory neuropathy type I (HSN1) is the most common dominantly inherited degenerative disorder of sensory neurons. The gene mutation was mapped to chromosome 9 in a large Australian family, descended from an ancestor from southern England who was a convict. Dawkins et al. recently reported gene mutations in the SPTLC1 gene, in this and other families. The first description of hereditary sensory neuropathy, by Hicks, was in a family from London and Exeter. To determine if the families in the present study that have SPTLC1 mutations are related to English families with HSN1 and, possibly, to the family studied by Hicks, we performed haplotype analysis of four Australian families of English extraction, four English families, and one Austrian family. Three Australian families of English extraction and three English families (two of whom have been described elsewhere) had the 399T→G SPTLC1 mutation, the same chromosome 9 haplotype, and the same phenotype. The Australian and English families may therefore have a common founder who, on the basis of historical information, has been determined to have lived in southern England prior to 1800. The sensorimotor neuropathy phenotype caused by the 399T→G SPTLC1 mutation is the same as that reported by Campbell and Hoffman and, possibly, the same as that originally described by Hicks. PMID:11479835

  19. Auxin-regulated chromatin switch directs acquisition of flower primordium founder fate.

    PubMed

    Wu, Miin-Feng; Yamaguchi, Nobutoshi; Xiao, Jun; Bargmann, Bastiaan; Estelle, Mark; Sang, Yi; Wagner, Doris

    2015-01-01

    Reprogramming of cell identities during development frequently requires changes in the chromatin state that need to be restricted to the correct cell populations. Here we identify an auxin hormone-regulated chromatin state switch that directs reprogramming from transit amplifying to primordium founder cell fate in Arabidopsis inflorescences. Upon auxin sensing, the MONOPTEROS transcription factor recruits SWI/SNF chromatin remodeling ATPases to increase accessibility of the DNA for induction of key regulators of flower primordium initiation. In the absence of the hormonal cue, auxin sensitive Aux/IAA proteins bound to MONOPTEROS block recruitment of the SWI/SNF chromatin remodeling ATPases in addition to recruiting a co-repressor/histone deacetylase complex. This simple and elegant hormone-mediated chromatin state switch is ideally suited for iterative flower primordium initiation and orchestrates additional auxin-regulated cell fate transitions. Our findings establish a new paradigm for nuclear response to auxin. They also provide an explanation for how this small molecule can direct diverse plant responses. PMID:26460543

  20. MFN2 deletion of exons 7 and 8: founder mutation in the UK population.

    PubMed

    Carr, Aisling S; Polke, James M; Wilson, Jacob; Pelayo-Negro, Ana L; Laura, Matilde; Nanji, Tina; Holt, James; Vaughan, Jennifer; Rankin, Julia; Sweeney, Mary G; Blake, Julian; Houlden, Henry; Reilly, Mary M

    2015-06-01

    Mitofusin 2 (MFN2) mutations are the most common cause of axonal Charcot-Marie-Tooth disease (CMT2). The majority are inherited in an autosomal dominant manner but recessive and semi-dominant kindreds have also been described. We previously reported a deletion of exons 7 and 8 resulting in nonsense-mediated decay, segregating with disease when present in trans with another pathogenic MFN2 mutation. Detailed clinical and electrophysiological data on a series of five affected patients from four kindreds and, when available, their parents and relatives were collected. MFN2 Sanger sequencing, multiplex ligation probe amplification, and haplotype analysis were performed. A severe early-onset CMT phenotype was seen in all cases: progressive distal weakness, wasting, and sensory loss from infancy or early childhood. Optic atrophy (four of five) and wheelchair dependency in childhood were common (four of five). All were compound heterozygous for a deletion of exons 7 and 8 in MFN2 with another previously reported pathogenic mutation (Phe216Ser, Thr362Met, and Arg707Trp). Carrier parents and relatives were unaffected (age range: 24-82 years). Haplotype analysis confirmed that the deletion had a common founder in all families.

  1. Welander distal myopathy caused by an ancient founder mutation in TIA1 associated with perturbed splicing.

    PubMed

    Klar, Joakim; Sobol, Maria; Melberg, Atle; Mäbert, Katrin; Ameur, Adam; Johansson, Anna C V; Feuk, Lars; Entesarian, Miriam; Orlén, Hanna; Casar-Borota, Olivera; Dahl, Niklas

    2013-04-01

    Welander distal myopathy (WDM) is an adult onset autosomal dominant disorder characterized by distal limb weakness, which progresses slowly from the fifth decade. All WDM patients are of Swedish or Finnish descent and share a rare chromosome 2p13 haplotype. We restricted the WDM-associated haplotype followed by whole exome sequencing. Within the conserved haplotype, we identified a single heterozygous mutation c.1150G>A (p.E384K) in T-cell intracellular antigen-1 (TIA1) in all WDM patients investigated (n = 43). The TIA1 protein regulates splicing, and translation through direct interaction with mRNA and the p.E384K mutation is located in the C-terminal Q-rich domain that interacts with the U1-C splicing factor. TIA1 has been shown to prevent skipping of SMN2 exon 7, and we show that WDM patients have increased levels of spliced SMN2 in skeletal muscle cells when compared with controls. Immunostaining of WDM muscle biopsies showed accumulation of TIA1 and stress granulae proteins adjacent to intracellular inclusions, a typical finding in WDM. The combined findings strongly suggest that the TIA1 mutation causes perturbed RNA splicing and cellular stress resulting in WDM. The selection against the mutation is likely to be negligible and the age of the TIA1 founder mutation was calculated to approximately 1,050 years, which coincides with the epoch of early seafaring across the Baltic Sea.

  2. [THE FOUNDERS OF FIRST CHAIRS OF HISTORY OF MEDICINE AND SOCIAL HYGIENE IN THE USSR].

    PubMed

    Gorelova, L E; Kasimovskaia, N A

    2015-01-01

    The USSR academy of medical sciences was organized in 1944. At the same year, the institute of health care organization, medical statistics and social hygiene was included in its structure. Before the institute global tasks in area of research and pedagogic activities were stated. They were implemented in accordance with actual national demands. The institute became a leading research center of studying problems of population health, social hygiene, organization and management of health care and history of medicine. In 2003, the institute was renamed in the The RAMS national research institute of public health, and in 2013 was handed over the Federal agency of research organizations (FANO) of Russia. The directors of the institute were well-known scientists in the field of social hygiene health care organization and history of medicine. They made a significant input into development of medical education, combining scientific, managerial and pedagogic activities. The founders of the first chairs of history of medicine and social hygiene were the directors of the institute I.D. Strashun and N.A. Semashko. PMID:26411172

  3. Auxin-regulated chromatin switch directs acquisition of flower primordium founder fate.

    PubMed

    Wu, Miin-Feng; Yamaguchi, Nobutoshi; Xiao, Jun; Bargmann, Bastiaan; Estelle, Mark; Sang, Yi; Wagner, Doris

    2015-10-13

    Reprogramming of cell identities during development frequently requires changes in the chromatin state that need to be restricted to the correct cell populations. Here we identify an auxin hormone-regulated chromatin state switch that directs reprogramming from transit amplifying to primordium founder cell fate in Arabidopsis inflorescences. Upon auxin sensing, the MONOPTEROS transcription factor recruits SWI/SNF chromatin remodeling ATPases to increase accessibility of the DNA for induction of key regulators of flower primordium initiation. In the absence of the hormonal cue, auxin sensitive Aux/IAA proteins bound to MONOPTEROS block recruitment of the SWI/SNF chromatin remodeling ATPases in addition to recruiting a co-repressor/histone deacetylase complex. This simple and elegant hormone-mediated chromatin state switch is ideally suited for iterative flower primordium initiation and orchestrates additional auxin-regulated cell fate transitions. Our findings establish a new paradigm for nuclear response to auxin. They also provide an explanation for how this small molecule can direct diverse plant responses.

  4. CLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration

    PubMed Central

    Schaffer, Ashleigh E.; Eggens, Veerle R.C.; Caglayan, Ahmet Okay; Reuter, Miriam S.; Scott, Eric; Coufal, Nicole G.; Silhavy, Jennifer L.; Xue, Yuanchao; Kayserili, Hulya; Yasuno, Katsuhito; Rosti, Rasim Ozgur; Abdellateef, Mostafa; Caglar, Caner; Kasher, Paul R.; Cazemier, J. Leonie; Weterman, Marian A.; Cantagrel, Vincent; Cai, Na; Zweier, Christiane; Altunoglu, Umut; Satkin, N. Bilge; Aktar, Fesih; Tuysuz, Beyhan; Yalcinkaya, Cengiz; Caksen, Huseyin; Bilguvar, Kaya; Fu, Xiang-Dong; Trotta, Christopher; Gabriel, Stacey; Reis, André; Gunel, Murat; Baas, Frank; Gleeson, Joseph G.

    2014-01-01

    SUMMARY Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of over 2000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild type but not mutant human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data links tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans. PMID:24766810

  5. Auxin-regulated chromatin switch directs acquisition of flower primordium founder fate

    PubMed Central

    Wu, Miin-Feng; Yamaguchi, Nobutoshi; Xiao, Jun; Bargmann, Bastiaan; Estelle, Mark; Sang, Yi; Wagner, Doris

    2015-01-01

    Reprogramming of cell identities during development frequently requires changes in the chromatin state that need to be restricted to the correct cell populations. Here we identify an auxin hormone-regulated chromatin state switch that directs reprogramming from transit amplifying to primordium founder cell fate in Arabidopsis inflorescences. Upon auxin sensing, the MONOPTEROS transcription factor recruits SWI/SNF chromatin remodeling ATPases to increase accessibility of the DNA for induction of key regulators of flower primordium initiation. In the absence of the hormonal cue, auxin sensitive Aux/IAA proteins bound to MONOPTEROS block recruitment of the SWI/SNF chromatin remodeling ATPases in addition to recruiting a co-repressor/histone deacetylase complex. This simple and elegant hormone-mediated chromatin state switch is ideally suited for iterative flower primordium initiation and orchestrates additional auxin-regulated cell fate transitions. Our findings establish a new paradigm for nuclear response to auxin. They also provide an explanation for how this small molecule can direct diverse plant responses. DOI: http://dx.doi.org/10.7554/eLife.09269.001 PMID:26460543

  6. Chronic intestinal pseudo-obstruction in a child harboring a founder Hirschsprung RET mutation.

    PubMed

    Rossi, Valentina; Mosconi, Manuela; Nozza, Paolo; Murgia, Daniele; Mattioli, Girolamo; Ceccherini, Isabella; Pini Prato, Alessio

    2016-09-01

    Chronic intestinal pseudo obstruction (CIPO) is a rare clinical entity characterized by symptoms and signs of intestinal obstruction without either recognizable anatomical abnormalities or intestinal aganglionosis. A Chinese female infant presented to our institution with a clinical diagnosis of CIPO. Aganglionosis was ruled out by full thickness colonic and ileal biopsies and by rectal suction biopsies. Unexpectedly, direct sequencing and PCR amplification of RET proto-oncogene from peripheral blood extracted DNA identified a RET R114H mutation. This mutation has already been reported as strongly associated with Asian patients affected by Hirschsprung's disease (HSCR) and is considered a founder mutation in Asia. The same mutation has never been reported in patients with CIPO, so far. These findings support the role of RET in the development of the enteric nervous system but underline the importance of other genetic or environmental factors contributing to the gastrointestinal phenotype of the disease. Somehow, this RET R114H mutation proved to have a role in the etiology of both CIPO and HSCR and could contribute to a more diffuse imbalance of gut dysmotility. © 2016 Wiley Periodicals, Inc. PMID:27273837

  7. Hereditary sensory neuropathy type I: haplotype analysis shows founders in southern England and Europe.

    PubMed

    Nicholson, G A; Dawkins, J L; Blair, I P; Auer-Grumbach, M; Brahmbhatt, S B; Hulme, D J

    2001-09-01

    Hereditary sensory neuropathy type I (HSN1) is the most common dominantly inherited degenerative disorder of sensory neurons. The gene mutation was mapped to chromosome 9 in a large Australian family, descended from an ancestor from southern England who was a convict. Dawkins et al. recently reported gene mutations in the SPTLC1 gene, in this and other families. The first description of hereditary sensory neuropathy, by Hicks, was in a family from London and Exeter. To determine if the families in the present study that have SPTLC1 mutations are related to English families with HSN1 and, possibly, to the family studied by Hicks, we performed haplotype analysis of four Australian families of English extraction, four English families, and one Austrian family. Three Australian families of English extraction and three English families (two of whom have been described elsewhere) had the 399T-->G SPTLC1 mutation, the same chromosome 9 haplotype, and the same phenotype. The Australian and English families may therefore have a common founder who, on the basis of historical information, has been determined to have lived in southern England prior to 1800. The sensorimotor neuropathy phenotype caused by the 399T-->G SPTLC1 mutation is the same as that reported by Campbell and Hoffman and, possibly, the same as that originally described by Hicks. PMID:11479835

  8. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

    PubMed Central

    Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S. Munir; Boyd, Scott D.; Fire, Andrew Z.; Roskin, Krishna M.; Schramm, Chaim A.; Zhang, Zhenhai; Zhu, Jiang; Shapiro, Lawrence; Mullikin, James C.; Gnanakaran, S.; Hraber, Peter; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Cohen, Myron; Kaminga, Gift; Louder, Mark K.; Tran, Lillan M.; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, Gordon M.; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Shaw, George M.; Hahn, Beatrice H.; Kepler, Thomas B.; Korber, Bette T.M.; Kwong, Peter D.; Mascola, John R.; Haynes, Barton F.

    2013-01-01

    Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in ~20% of HIV-1-infected individuals, and details of their generation could provide a roadmap for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from time of infection. The mature antibody, CH103, neutralized ~55% of HIV-1 isolates, and its co-crystal structure with gp120 revealed a novel loop-based mechanism of CD4-binding site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the CH103-lineage unmutated common ancestor avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data elucidate the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies and provide insights into strategies to elicit similar antibodies via vaccination. PMID:23552890

  9. Willet M. Hays, great benefactor to plant breeding and the founder of our association.

    PubMed

    Troyer, A F; Stoehr, H

    2003-01-01

    Willet M. Hays was a great benefactor to plant breeding and the founder of the American Genetic Association (AGA). We commemorate the AGA's centennial. We mined university archives, U.S. Department of Agriculture (USDA) yearbooks, plant breeding textbooks, scientific periodicals, and descendants for information. Willet Hays first recognized the individual plant as the unit of selection and started systematic pure-line selection and progeny tests in 1888. He developed useful plant breeding methods. He selected superior flax (Linum usitatissimum L.), wheat (Triticum vulgare L.), corn (Zea mays L.), barley (Hordeum vulgare L.), and oat (Avena sativa L.) varieties, and discovered Grimm alfalfa (Medicago sativa L.); all became commercially important. He initiated branch stations for better performance testing. Willet Hays befriended colleagues in other universities, in federal stations, in a London conference, and in Europe. He gathered and spread the scientific plant breeding gospel. He also improved rural roads and initiated animal breeding records and agricultural economics records. He started the AGA in 1903, serving as secretary for 10 years. He became assistant secretary of agriculture in 1904. He introduced the project system for agricultural research. He authored or coauthored the Nelson Amendment, the Smith-Lever Act, the Smith-Hughes Act, and the protocol leading to the United Nations Food and Agriculture Organization-all involved teaching agricultural practices that improved the world. PMID:14691309

  10. Founders, drift, and infidelity: the relationship between Y chromosome diversity and patrilineal surnames.

    PubMed

    King, Turi E; Jobling, Mark A

    2009-05-01

    Most heritable surnames, like Y chromosomes, are passed from father to son. These unique cultural markers of coancestry might therefore have a genetic correlate in shared Y chromosome types among men sharing surnames, although the link could be affected by mutation, multiple foundation for names, nonpaternity, and genetic drift. Here, we demonstrate through an analysis of 1,678 Y-chromosomal haplotypes within 40 British surnames a remarkably high degree of coancestry that generally increases as surnames become rarer. On average, the proportion of haplotypes lying within descent clusters is 62% but ranges from 0% to 87%. The shallow time depth of many descent clusters within names, the lack of a detectable effect of surname derivation on diversity, and simulations of surname descent suggest that genetic drift through variation in reproductive success is important in structuring haplotype diversity. Modern patterns therefore provide little reliable information about the original founders of surnames some 700 years ago. A comparative analysis of published data on Y diversity within Irish surnames demonstrates a relative lack of surname frequency dependence of coancestry, a difference probably mediated through distinct Irish and British demographic histories including even more marked genetic drift in Ireland.

  11. [On the founders of the Institute of Mathematics and Physics, University of Bahia].

    PubMed

    Dias, A L

    The reduced number of female students of mathematics at the University of Bahia School of Philosophy (Faculdade de Filosofia, Universidade da Bahia - FF/UBa) is quite surprising. To date, they are concentrated in areas traditionally viewed as feminine whereas men predominate in the mathematical fields. I have examined interview data from a few women who graduated in mathematics and went on to teach at the University of Bahia School of Mathematics (Faculdade de Filosofia - FF) and at the Institute of Mathematics and Physics (Instituto de Matemática e Física - IMF), where they were soon to outnumber men and constitute the majority of the mathematics teaching staff. In this study, I have investigated the course of their careers over time: from their early student days, through their time as teaching assistants and professors, and finally as founders of the Institute of Mathematics and Physics, in 1960. Special reference is made to Martha Maria de Souza Dantas, organizer of the I Brazilian Conference on Mathematics Teaching, an event which has provided the groundwork for what was to become the Institute (IMF); and to Arlete Cerqueira Lima, the mastermind behind its creation.

  12. Founders, Drift, and Infidelity: The Relationship between Y Chromosome Diversity and Patrilineal Surnames

    PubMed Central

    King, Turi E.

    2009-01-01

    Most heritable surnames, like Y chromosomes, are passed from father to son. These unique cultural markers of coancestry might therefore have a genetic correlate in shared Y chromosome types among men sharing surnames, although the link could be affected by mutation, multiple foundation for names, nonpaternity, and genetic drift. Here, we demonstrate through an analysis of 1,678 Y-chromosomal haplotypes within 40 British surnames a remarkably high degree of coancestry that generally increases as surnames become rarer. On average, the proportion of haplotypes lying within descent clusters is 62% but ranges from 0% to 87%. The shallow time depth of many descent clusters within names, the lack of a detectable effect of surname derivation on diversity, and simulations of surname descent suggest that genetic drift through variation in reproductive success is important in structuring haplotype diversity. Modern patterns therefore provide little reliable information about the original founders of surnames some 700 years ago. A comparative analysis of published data on Y diversity within Irish surnames demonstrates a relative lack of surname frequency dependence of coancestry, a difference probably mediated through distinct Irish and British demographic histories including even more marked genetic drift in Ireland. PMID:19204044

  13. [HUGO STEINHAUS--CO-FOUNDER OF THE LWÓW SCHOOL OF MATHEMATICS].

    PubMed

    Wócik, Wiesław

    2014-01-01

    The paper is dedicated to the presentation of professor Hugo Steinhaus--co-founder of the Lwów School of Mathematics. It is indicated that had it not been for the scholar, the founding and development of the Lwów School of Mathematics would have been almost impossible. The analyses focus on his undertakings during the Lvov period in the early 1920s and those events that preceded the founding of the school (namely Steinhaus's education at the Göttingen University, various meetings and gatherings, discussions, first fascinations and mathematical dissertations). This paper, however, does not look into the scientific output of Steinhaus, only presents his method of scientific work and highlights the strategy that he chose in order to create the scientific community. An attempt has been also made to justify the effectiveness of the adopted strategy by describing the scientific atmosphere of Lvov and intellectual potential of the students of the school. Steinhaus's activities in the 1930s will be only marginally presented with an impact on particularly interesting cooperation with the alumni of the Lwów School of Mathematics--Marek Kac, Stefan Kaczmarz, Paweł Nikliborec and scholars from other fields of science (as part of the process of the application of mathematics).

  14. Linkage disequilibrium analysis in young populations: pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians.

    PubMed

    Labuda, M; Labuda, D; Korab-Laskowska, M; Cole, D E; Zietkiewicz, E; Weissenbach, J; Popowska, E; Pronicka, E; Root, A W; Glorieux, F H

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be approximately 12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbrück model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. PMID:8751865

  15. Identification of full-length transmitted/founder viruses and their progeny in primary HIV-1 infection

    SciTech Connect

    Korber, Bette; Hraber, Peter; Giorgi, Elena; Bhattacharya, T

    2009-01-01

    Identification of transmitted/founder virus genomes and their progeny by is a novel strategy for probing the molecular basis of HIV-1 transmission and for evaluating the genetic imprint of viral and host factors that act to constrain or facilitate virus replication. Here, we show in a cohort of twelve acutely infected subjects (9 clade B; 3 clade C), that complete genomic sequences of transmitted/founder viruses could be inferred using single genome amplification of plasma viral RNA, direct amplicon sequencing, and a model of random virus evolution. This allowed for the precise identification, chemical synthesis, molecular cloning, and biological analysis of those viruses actually responsible for productive clinical infection and for a comprehensive mapping of sequential viral genomes and proteomes for mutations that are necessary or incidental to the establishment of HIV-1 persistence. Transmitted/founder viruses were CD4 and CCR5 tropic, replicated preferentially in activated primary T-Iymphocytes but not monocyte-derived macrophages, and were effectively shielded from most heterologous or broadly neutralizing antibodies. By 3 months of infection, the evolving viral quasispecies in three subjects showed mutational fixation at only 2-5 discreet genomic loci. By 6-12 months, mutational fixation was evident at 18-27 genomic loci. Some, but not all, of these mutations were attributable to virus escape from cytotoxic Tlymphocytes or neutralizing antibodies, suggesting that other viral or host factors may influence early HIV -1 fitness.

  16. Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis.

    PubMed

    Bu, Rong; Siraj, Abdul K; Al-Obaisi, Khadija A S; Beg, Shaham; Al Hazmi, Mohsen; Ajarim, Dahish; Tulbah, Asma; Al-Dayel, Fouad; Al-Kuraya, Khawla S

    2016-09-01

    Ethnic differences of breast cancer genomics have prompted us to investigate the spectra of BRCA1 and BRCA2 mutations in different populations. The prevalence and effect of BRCA 1 and BRCA 2 mutations in Middle Eastern population is not fully explored. To characterize the prevalence of BRCA mutations in Middle Eastern breast cancer patients, BRCA mutation screening was performed in 818 unselected breast cancer patients using Capture and/or Sanger sequencing. 19 short tandem repeat (STR) markers were used for founder mutation analysis. In our study, nine different types of deleterious mutation were identified in 28 (3.4%) cases, 25 (89.3%) cases in BRCA 1 and 3 (10.7%) cases in BRCA 2. Seven recurrent mutations identified accounted for 92.9% (26/28) of all the mutant cases. Haplotype analysis was performed to confirm c.1140 dupG and c.4136_4137delCT mutations as novel putative founder mutation, accounting for 46.4% (13/28) of all BRCA mutant cases and 1.6% (13/818) of all the breast cancer cases, respectively. Moreover, BRCA 1 mutation was significantly associated with BRCA 1 protein expression loss (p = 0.0005). Our finding revealed that a substantial number of BRCA mutations were identified in clinically high risk breast cancer from Middle East region. Identification of the mutation spectrum, prevalence and founder effect in Middle Eastern population facilitates genetic counseling, risk assessment and development of cost-effective screening strategy.

  17. Diversification in the tropical pacific: comparisons between marine and terrestrial systems and the importance of founder speciation.

    PubMed

    Paulay, Gustav; Meyer, Chris

    2002-11-01

    Patterns of distribution and processes of differentiation have often been contrasted between terrestrial and marine biotas. The islands of Oceania offer an excellent setting to explore this contrast, because the geographic setting for terrestrial and shallow-water, benthic, marine organisms are the same: the myriad islands strewn across the vast Pacific. The size of species ranges and the geographic distribution of endemism are two biogeographic attributes that are thought to differ markedly between terrestrial and marine biotas in the Pacific. While terrestrial species are frequently confined to single islands or archipelagoes throughout Oceania, marine species tend to have wide to very wide distributions, and are rarely restricted to single island groups except for the most isolated archipelagoes. We explore the conditions under which species can reach an island by dispersal and differentiate. Genetic differentiation can occur either through founder speciation or vicariance; these processes are requisite ends of a continuum. We show that founder speciation is most likely when few propagules enter the dispersal medium and survive well while they travel far. We argue that conditions favorable to founder speciation are common in marine as well as terrestrial systems, and that terrestrial-type, archipelagic-level endemism is likely common in marine taxa. We give examples of marine groups that show archipelagic level endemism on most Pacific island groups as well as of terrestrial species that are widespread. Thus both the patterns and processes of insular diversification are variable, and overlap more between land and sea than previously considered. PMID:21680372

  18. Investigations of the Y Chromosome, Male Founder Structure and YSTR Mutation Rates in the Old Order Amish

    PubMed Central

    Pollin, Toni I.; McBride, Daniel J.; Agarwala, Richa; Schäffer, Alejandro A.; Shuldiner, Alan R.; Mitchell, Braxton D.; O'Connell, Jeffrey R.

    2007-01-01

    Objectives Using Y chromosome short tandem repeat (YSTR) genotypes, (1) evaluate the accuracy and completeness of the Lancaster County Old Order Amish (OOA) genealogical records and (2) estimate YSTR mutation rates. Methods Nine YSTR markers were genotyped in 739 Old Order Amish males who participated in several ongoing genetic studies of complex traits and could be connected into one of 28 all-male lineage pedigrees constructed using the Anabaptist Genealogy Database and the query software PedHunter. A putative founder YSTR haplotype was constructed for each pedigree, and observed and inferred father-son transmissions were used to estimate YSTR mutation rates. Results We inferred 27 distinct founder Y chromosome haplotypes in the 28 male lineages, which encompassed 27 surnames accounting for 98% of Lancaster OOA households. Nearly all deviations from founder haplotypes were consistent with mutation events rather than errors. The estimated marker-specific mutation rates ranged from 0 to 1.09% (average 0.33% using up to 283 observed meioses only and 0.28% using up to 1,232 observed and inferred meioses combined). Conclusions These data confirm the accuracy and completeness of the male lineage portion of the Anabaptist Genealogy Database and contribute mutation rate estimates for several commonly used Y chromosome STR markers. PMID:17898540

  19. Diversification in the tropical pacific: comparisons between marine and terrestrial systems and the importance of founder speciation.

    PubMed

    Paulay, Gustav; Meyer, Chris

    2002-11-01

    Patterns of distribution and processes of differentiation have often been contrasted between terrestrial and marine biotas. The islands of Oceania offer an excellent setting to explore this contrast, because the geographic setting for terrestrial and shallow-water, benthic, marine organisms are the same: the myriad islands strewn across the vast Pacific. The size of species ranges and the geographic distribution of endemism are two biogeographic attributes that are thought to differ markedly between terrestrial and marine biotas in the Pacific. While terrestrial species are frequently confined to single islands or archipelagoes throughout Oceania, marine species tend to have wide to very wide distributions, and are rarely restricted to single island groups except for the most isolated archipelagoes. We explore the conditions under which species can reach an island by dispersal and differentiate. Genetic differentiation can occur either through founder speciation or vicariance; these processes are requisite ends of a continuum. We show that founder speciation is most likely when few propagules enter the dispersal medium and survive well while they travel far. We argue that conditions favorable to founder speciation are common in marine as well as terrestrial systems, and that terrestrial-type, archipelagic-level endemism is likely common in marine taxa. We give examples of marine groups that show archipelagic level endemism on most Pacific island groups as well as of terrestrial species that are widespread. Thus both the patterns and processes of insular diversification are variable, and overlap more between land and sea than previously considered.

  20. Linkage disequilibrium analysis in young populations: Pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians

    SciTech Connect

    Labuda, M.; Glorieux, F.H.; Labuda, D.; Korab-Laskowska, M.

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be {approximately}12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbruck model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. 48 refs., 5 figs., 2 tabs.

  1. Estimation of the number of founders of an invasive pest insect population: the fire ant Solenopsis incivta in the United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Determination of the number of founders responsible for the establishment of invasive plant and animal populations is important for developing biologically based management practices, predicting the invasive potential of species, and making inferences about basic ecological and evolutionary processe...

  2. Testing founder effect speciation: Divergence population genetics of the Spoonbills Platalea regia and Pl. minor (Threskiornithidae, Aves)

    USGS Publications Warehouse

    Yeung, Carol K.L.; Tsai, Pi-Wen; Chesser, R. Terry; Lin, Rong-Chien; Yao, Cheng-Te; Tian, Xiu-Hua; Li, Shou-Hsien

    2011-01-01

    Although founder effect speciation has been a popular theoretical model for the speciation of geographically isolated taxa, its empirical importance has remained difficult to evaluate due to the intractability of past demography, which in a founder effect speciation scenario would involve a speciational bottleneck in the emergent species and the complete cessation of gene flow following divergence. Using regression-weighted approximate Bayesian computation, we tested the validity of these two fundamental conditions of founder effect speciation in a pair of sister species with disjunct distributions: the royal spoonbill Platalea regia in Australasia and the black-faced spoonbill Pl. minor in eastern Asia. When compared with genetic polymorphism observed at 20 nuclear loci in the two species, simulations showed that the founder effect speciation model had an extremely low posterior probability (1.55 × 10-8) of producing the extant genetic pattern. In contrast, speciation models that allowed for postdivergence gene flow were much more probable (posterior probabilities were 0.37 and 0.50 for the bottleneck with gene flow and the gene flow models, respectively) and postdivergence gene flow persisted for a considerable period of time (more than 80% of the divergence history in both models) following initial divergence (median = 197,000 generations, 95% credible interval [CI]: 50,000-478,000, for the bottleneck with gene flow model; and 186,000 generations, 95% CI: 45,000-477,000, for the gene flow model). Furthermore, the estimated population size reduction in Pl. regia to 7,000 individuals (median, 95% CI: 487-12,000, according to the bottleneck with gene flow model) was unlikely to have been severe enough to be considered a bottleneck. Therefore, these results do not support founder effect speciation in Pl. regia but indicate instead that the divergence between Pl. regia and Pl. minor was probably driven by selection despite continuous gene flow. In this light, we

  3. Susceptibility to quantum dot induced lung inflammation differs widely among the Collaborative Cross founder mouse strains.

    PubMed

    Scoville, David K; White, Collin C; Botta, Dianne; McConnachie, Lisa A; Zadworny, Megan E; Schmuck, Stefanie C; Hu, Xiaoge; Gao, Xiaohu; Yu, Jianbo; Dills, Russell L; Sheppard, Lianne; Delaney, Martha A; Griffith, William C; Beyer, Richard P; Zangar, Richard C; Pounds, Joel G; Faustman, Elaine M; Kavanagh, Terrance J

    2015-12-01

    Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci. PMID:26476918

  4. A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy.

    PubMed

    Hicks, Debbie; Sarkozy, A; Muelas, N; Koehler, K; Huebner, A; Hudson, G; Chinnery, P F; Barresi, R; Eagle, M; Polvikoski, T; Bailey, G; Miller, J; Radunovic, A; Hughes, P J; Roberts, R; Krause, S; Walter, M C; Laval, S H; Straub, V; Lochmüller, H; Bushby, K

    2011-01-01

    The limb-girdle muscular dystrophies are a group of disorders with wide genetic and clinical heterogeneity. Recently, mutations in the ANO5 gene, which encodes a putative calcium-activated chloride channel belonging to the Anoctamin family of proteins, were identified in five families with one of two previously identified disorders, limb-girdle muscular dystrophy 2L and non-dysferlin Miyoshi muscular dystrophy. We screened a candidate group of 64 patients from 59 British and German kindreds and found the truncating mutation, c.191dupA in exon 5 of ANO5 in 20 patients, homozygously in 15 and in compound heterozygosity with other ANO5 variants in the rest. An intragenic single nucleotide polymorphism and an extragenic microsatellite marker are in linkage disequilibrium with the mutation, suggesting a founder effect in the Northern European population. We have further defined the clinical phenotype of ANO5-associated muscular dystrophy. Patients show adult onset proximal lower limb weakness with highly raised serum creatine kinase values (average 4500 IU/l) and frequent muscle atrophy and asymmetry of muscle involvement. Onset varies from the early 20 s to 50 s and the weakness is generally slowly progressive, with most patients remaining ambulant for several decades. Distal presentation is much less common but a milder degree of distal lower limb weakness is often observed. Upper limb strength is only mildly affected and cardiac and respiratory function is normal. Females appear less frequently affected. In the North of England population we have identified eight patients with ANO5 mutations, suggesting a minimum prevalence of 0.27/100,000, twice as common as dysferlinopathy. We suggest that mutations in ANO5 represent a relatively common cause of adult onset muscular dystrophy with high serum creatine kinase and that mutation screening, particularly of the common mutation c.191dupA, should be an early step in the diagnostic algorithm of adult limb-girdle muscular

  5. Comprehensive Characterization of the Transmitted/founder env Genes from a Single MSM Cohort in China

    PubMed Central

    Chen, Yue; Li, Ning; Zhang, Tong; Huang, Xiaojie; Cai, Fangping; Vandergrift, Nathan; Xin, Ruolei; Meng, Zhefeng; Zhang, Xiaoyan; Jiang, Chunlai; Xu, Xiaoning; Montefiori, David C; Gao, Feng; Wu, Hao

    2015-01-01

    Background The men having sex with men (MSM) population has become one of major risk groups for HIV-1 infection in China. However, the epidemiological patterns, function of the env genes, and autologous and heterologous neutralization activity in the same MSM population have not been systematically characterized. Methods The env gene sequences were obtained by the single genome amplification (SGA). The time to the most recent common ancestor (tMRCA) was estimated for each genotype using the Bayesian MCMC approach. Coreceptor usage was determined in NP-2 cells. Neutralization was analyzed using Env pseudoviruses in TZM-bl cells. Results We have obtained 547 full-length env gene sequences by SGA from 30 acute/early HIV-1-infected individuals in the Beijing MSM cohort. Three genotypes (Subtype B, CRF01_AE, and CRF07_BC) were identified and 20% of the individuals were infected with multiple transmitted/founder (T/F) viruses. The tight clusters of the MSM sequences regardless of geographic origins indicated nearly exclusive transmission within the MSM population and limited number of introductions. The tMRCA for each genotype was 10-15 years after each was first introduced in China. Disparate preferences for coreceptor usages among three genotypes might lead to the changes in percentage of different genotypes in the MSM population over time. The genotype-matched and -mismatched neutralization activity varied among the three genotypes. Conclusions Identification of unique characteristics for transmission, coreceptor usage, neutralization profile and epidemic patterns of HIV-1 is critical for the better understanding of transmission mechanisms, development of preventive strategies, and evaluation of vaccine efficacy in the MSM population in China. PMID:25886933

  6. Counting the Founders: The Matrilineal Genetic Ancestry of the Jewish Diaspora

    PubMed Central

    Behar, Doron M.; Metspalu, Ene; Kivisild, Toomas; Rosset, Saharon; Tzur, Shay; Hadid, Yarin; Yudkovsky, Guennady; Rosengarten, Dror; Pereira, Luisa; Amorim, Antonio; Kutuev, Ildus; Gurwitz, David; Bonne-Tamir, Batsheva; Villems, Richard; Skorecki, Karl

    2008-01-01

    The history of the Jewish Diaspora dates back to the Assyrian and Babylonian conquests in the Levant, followed by complex demographic and migratory trajectories over the ensuing millennia which pose a serious challenge to unraveling population genetic patterns. Here we ask whether phylogenetic analysis, based on highly resolved mitochondrial DNA (mtDNA) phylogenies can discern among maternal ancestries of the Diaspora. Accordingly, 1,142 samples from 14 different non-Ashkenazi Jewish communities were analyzed. A list of complete mtDNA sequences was established for all variants present at high frequency in the communities studied, along with high-resolution genotyping of all samples. Unlike the previously reported pattern observed among Ashkenazi Jews, the numerically major portion of the non-Ashkenazi Jews, currently estimated at 5 million people and comprised of the Moroccan, Iraqi, Iranian and Iberian Exile Jewish communities showed no evidence for a narrow founder effect, which did however characterize the smaller and more remote Belmonte, Indian and the two Caucasus communities. The Indian and Ethiopian Jewish sample sets suggested local female introgression, while mtDNAs in all other communities studied belong to a well-characterized West Eurasian pool of maternal lineages. Absence of sub-Saharan African mtDNA lineages among the North African Jewish communities suggests negligible or low level of admixture with females of the host populations among whom the African haplogroup (Hg) L0-L3 sub-clades variants are common. In contrast, the North African and Iberian Exile Jewish communities show influence of putative Iberian admixture as documented by mtDNA Hg HV0 variants. These findings highlight striking differences in the demographic history of the widespread Jewish Diaspora. PMID:18446216

  7. A founder mutation in Anoctamin 5 is a major cause of limb girdle muscular dystrophy

    PubMed Central

    Muelas, Nuria; Köehler, Katrin; Huebner, Angela; Hudson, Gavin; Chinnery, Patrick F.; Barresi, Rita; Eagle, Michelle; Polvikoski, Tuomo; Bailey, Geraldine; Miller, James; Radunovic, Aleksander; Hughes, Paul J.; Roberts, Richard; Krause, Sabine; Walter, Maggie C.; Laval, Steven H.; Straub, Volker; Lochmüller, Hanns; Bushby, Kate

    2014-01-01

    The limb girdle muscular dystrophies (LGMDs) are a group of disorders with wide genetic and clinical heterogeneity. Recently, mutations in the ANO5 gene, which encodes a putative calcium-activated chloride channel belonging to the Anoctamin family of proteins, were identified in five families with one of two previously identified disorders, LGMD2L and non-dysferlin Miyoshi muscular dystrophy (MMD3). We screened a candidate group of 64 patients from 59 British and German kindreds and found the truncating mutation, c.191dupA in exon 5 of ANO5 in 20 patients, homozygously in 15 and in compound heterozygosity with other ANO5 variants in the rest. An intragenic SNP and an extragenic microsatellite marker are in linkage disequilibrium with the mutation, suggesting a founder effect in the Northern European population. We have further defined the clinical phenotype of ANO5-associated muscular dystrophy. Patients show adult onset proximal lower limb weakness with highly raised creatinine kinase (CK) values (average 4500 IU/l) and frequent muscle atrophy and asymmetry of muscle involvement. Onset varies from the early 20s to 50s and the weakness is generally slowly progressive, with most patients remaining ambulant for several decades. Distal presentation is much less common but a milder degree of distal lower limb weakness is often observed. Upper limb strength is only mildly affected and cardiac and respiratory function is normal. Females appear less frequently affected. In the North of England population we have identified eight patients with ANO5 mutations, suggesting a minimum prevalence of 0.27/100 000, twice as common as dysferlinopathy. We suggest that mutations in ANO5 represent a relatively common cause of adult onset muscular dystrophy with high CK and that mutation screening, particularly of the common mutation c.191dupA, should be an early step in the diagnostic algorithm of adult LGMD patients. PMID:21186264

  8. HIV competition dynamics over sexual networks: first comer advantage conserves founder effects.

    PubMed

    Ferdinandy, Bence; Mones, Enys; Vicsek, Tamás; Müller, Viktor

    2015-02-01

    Outside Africa, the global phylogeography of HIV is characterized by compartmentalized local epidemics that are typically dominated by a single subtype, which indicates strong founder effects. We hypothesized that the competition of viral strains at the epidemic level may involve an advantage of the resident strain that was the first to colonize a population. Such an effect would slow down the invasion of new strains, and thus also the diversification of the epidemic. We developed a stochastic modelling framework to simulate HIV epidemics over dynamic contact networks. We simulated epidemics in which the second strain was introduced into a population where the first strain had established a steady-state epidemic, and assessed whether, and on what time scale, the second strain was able to spread in the population. Simulations were parameterized based on empirical data; we tested scenarios with varying levels of overall prevalence. The spread of the second strain occurred on a much slower time scale compared with the initial expansion of the first strain. With strains of equal transmission efficiency, the second strain was unable to invade on a time scale relevant for the history of the HIV pandemic. To become dominant over a time scale of decades, the second strain needed considerable (>25%) advantage in transmission efficiency over the resident strain. The inhibition effect was weaker if the second strain was introduced while the first strain was still in its growth phase. We also tested how possible mechanisms of interference (inhibition of superinfection, depletion of highly connected hubs in the network, one-time acute peak of infectiousness) contribute to the inhibition effect. Our simulations confirmed a strong first comer advantage in the competition dynamics of HIV at the population level, which may explain the global phylogeography of the virus and may influence the future evolution of the pandemic.

  9. Foundering lithosphere triggers transient basins and backarc magmatism at subduction zones?

    NASA Astrophysics Data System (ADS)

    Wang, H.; Currie, C. A.; DeCelles, P. G.

    2015-12-01

    Many upper-plate processes at subduction zones cannot be directly explained by traditional subduction mechanisms. In the Central Andes, the crust is shortened and thickened by the subduction of Nazca plate, but the lower lithosphere is anomalously thin at present. Within the plateau, localized, transient basins have formed since the Miocene. These basins have experienced subsidence, internal shortening, and then inversion. One hypothesis is these basins are related to the formation and foundering of dense eclogite rocks in the lithosphere. Along the eastern plateau, there are sites of basaltic magmatism which show a gradual westward migration. Geochemistry studies suggest that these magmas are mainly caused by upwelling asthenosphere, indicating lithosphere thinning beneath this area. However, the magmas are landward of the basins, and therefore the formation and removal of the dense anomaly is spatially and temporally offset from the region of lithosphere thinning. In this study, 2D numerical models are used to investigate lithosphere removal within a subduction zone. A dense root is placed in lower crust of the upper plate to simulate the eclogitization process and initiate gravitational removal. The model evolves in three phases: 1) As the root becomes denser, the overlying surface subsides and a basin forms; 2) once the root is denser than mantle, it sinks and decouples from the upper plate. During this period, the basin inverts and uplifts. 3) Meanwhile, the mantle lithosphere landward of the root is sheared by the corner flow in the mantle wedge. As the lithosphere is carried trenchward, a gap forms at the landside of plateau which widens over time. Hot asthenosphere upwells to fill the gap and undergoes decompression melting. The model results are consistent with observations from the Central Andes and could have implications for other subduction regions with enigmatic transient basins and backarc magmatism, such as those in North America and Eastern China.

  10. The Significance of Genetic Polymorphisms within and between Founder Populations of Ceratitis capitata (Wied.) from Argentina

    PubMed Central

    Basso, Alicia; Martinez, Laura; Manso, Fanny

    2009-01-01

    Background The Mediterranean fruit fly Ceratitis Capitata (DIPTERA: Tephritidae) is a major agricultural pest in Argentina. One main cause for the success of non-contaminant control programs based on genetic strategies is compatibility between natural and laboratory germplasms. A comprehensive characterization of the fruit fly based on genetic studies and compatibility analysis was undertaken on two founder populations from the provinces of Buenos Aires and Mendoza, used in pioneering sterile male technique control programmes in our country. The locations are 1,000 km apart from each other. Methodology/Principal Findings We compared the genetic composition of both populations based on cytological, physiological and morphological characterization. Compatibility studies were performed in order to determine the presence of isolation barriers. Results indicate that the Buenos Aires germplasm described previously is partially different from that of the Mendoza population. Both laboratory colonies are a reservoir of mutational and cytological polymorphisms. Some sexual chromosome variants such as the XL and the YL resulting from attachment of a B-chromosome to the X-chromosome or Y-chromosome behave as a lethal sex-linked factor. Our results also show incompatibility between both germplasms and pre-zygotic isolation barriers between them. Our evidence is consistent with the fact that polymorphisms are responsible for the lack of compatibility. Conclusions The genetic control mechanism should be directly produced in the germplasm of the target population in order to favour mating conditions. This is an additional requirement for the biological as well as economic success of control programs based on genetic strategies such as the sterile insect technique. The analysis of representative samples also revealed natural auto-control mechanisms which could be used in modifying pest population dynamics. PMID:19252742

  11. HIV Competition Dynamics over Sexual Networks: First Comer Advantage Conserves Founder Effects

    PubMed Central

    Ferdinandy, Bence; Mones, Enys; Vicsek, Tamás; Müller, Viktor

    2015-01-01

    Outside Africa, the global phylogeography of HIV is characterized by compartmentalized local epidemics that are typically dominated by a single subtype, which indicates strong founder effects. We hypothesized that the competition of viral strains at the epidemic level may involve an advantage of the resident strain that was the first to colonize a population. Such an effect would slow down the invasion of new strains, and thus also the diversification of the epidemic. We developed a stochastic modelling framework to simulate HIV epidemics over dynamic contact networks. We simulated epidemics in which the second strain was introduced into a population where the first strain had established a steady-state epidemic, and assessed whether, and on what time scale, the second strain was able to spread in the population. Simulations were parameterized based on empirical data; we tested scenarios with varying levels of overall prevalence. The spread of the second strain occurred on a much slower time scale compared with the initial expansion of the first strain. With strains of equal transmission efficiency, the second strain was unable to invade on a time scale relevant for the history of the HIV pandemic. To become dominant over a time scale of decades, the second strain needed considerable (>25%) advantage in transmission efficiency over the resident strain. The inhibition effect was weaker if the second strain was introduced while the first strain was still in its growth phase. We also tested how possible mechanisms of interference (inhibition of superinfection, depletion of highly connected hubs in the network, one-time acute peak of infectiousness) contribute to the inhibition effect. Our simulations confirmed a strong first comer advantage in the competition dynamics of HIV at the population level, which may explain the global phylogeography of the virus and may influence the future evolution of the pandemic. PMID:25654450

  12. A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy.

    PubMed

    Toyota, Kentaro; Hashimoto, Taeko; Ogino, Daisuke; Matsunaga, Akira; Ito, Minoru; Masakane, Ikuto; Degawa, Noriyuki; Sato, Hiroshi; Shirai, Sayuri; Umetsu, Kazuo; Tamiya, Gen; Saito, Takao; Hayasaka, Kiyoshi

    2013-05-01

    Lipoprotein glomerulopathy (LPG) is a hereditary disease characterized by lipoprotein thrombi in the glomerulus, hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (APOE). More than 12 APOE mutations have been identified as causes of LPG, and APOE-Sendai (Arg145Pro) mutation was frequently detected in patients from the eastern part of Japan including Yamagata prefecture. Recently, effective therapy with intensive lipid-lowering agents was established, and epidemiologic data are required for early diagnosis. We determined the haplotype structure of APOE-Sendai in 13 patients from 9 unrelated families with LPG, and found that the haplotype of all APOE-Sendai mutations was identical, suggesting that APOE-Sendai mutation is common in Japanese patients probably through a founder effect. We also studied the gene frequency of APOE-Sendai in 2023 control subjects and 418 patients receiving hemodialysis in Yamagata prefecture using the TaqMan method, but did not identify any subjects carrying the mutation, indicating that it is very rare in the general population even in the eastern part of Japan. In addition to APOE mutation, other genetic and/or epigenetic factors are considered to be involved in the pathogenesis of LPG because of its low penetrance. The patients did not have a common haplotype of the counterpart APOE allele, and some patients had the same haplotype of the counterpart APOE allele as the asymptomatic carriers. These results suggest that the counterpart APOE allele is not likely associated with the onset of LPG. Further study is required to clarify the pathogenesis of LPG.

  13. Particular Mal de Meleda phenotypes in Tunisia and mutations founder effect in the Mediterranean region.

    PubMed

    Bchetnia, Mbarka; Laroussi, Nadia; Youssef, Monia; Charfeddine, Cherine; Ben Brick, Ahlem Sabrine; Boubaker, Mohamed Samir; Mokni, Mourad; Abdelhak, Sonia; Zili, Jameleddine; Benmously, Rym

    2013-01-01

    Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles that progressively extend to the dorsal surface of the hands and feet. It is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1). We performed mutational analysis by direct sequencing of SLURP-1 gene in order to identify the genetic defect in three unrelated families (families MDM-12, MDM-13, and MDM-14) variably affected with transgressive palmoplantar keratoderma. A spectrum of clinical presentations with variable features has been observed from the pronounced to the transparent hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr variation is only described in Tunisian families making evidence of founder effect mutation of likely Tunisian origin. Our patients presented with very severe to relatively mild phenotypes, including multiple keratolytic pits observed for one patient in the hyperkeratotic area which was not previously reported. The phenotypic variability may reflect the influence of additional factors on disease characteristics. This report further expands the spectrum of clinical phenotypes associated with mutations in SLURP1 in the Mediterranean population.

  14. [Edward Wilhelm Drescher--the founder of pediatric surgery in West Pomerania].

    PubMed

    Pacanowski, J H

    1999-01-01

    Professor Edward Wilhelm Drescher--an eminent Polish pediatric surgeon and pioneer of this specialization in West Pomerania--was born in 1912 in Biłgoraj. His young years he spent in his parents familial town Kalisz, where he attended a very famous college--State Humanistic Grammar-School. In 1937 he graduated from Faculty of Medicine at the Warsaw University. Next year he started his career as a surgeon in the Surgery at Orthopedic Ward of Pediatric Clinic in Warsaw, which was directed by prof. Jan Kossakowski--excellent pediatric surgeon and artist. During the September Campaign he took part in the battle of Bzura and in the defense of Polish capital as the physician in the 25th Regiment of Artillery. In 1940 he joined Polish underground army--AK. In 1944, when the Warsaw Uprising broke out, he was the Commander of the insurgent hospital--Poznańska 11. It was a very well arranged and headed hospital, which admitted about eight hundred wounded soldiers and civilians. After the war for two years he lived in Sopot, where he organized and directed the Surgery Hospital and the Town Outpatients' Department. In 1947 he moved to Szczecin, where he arranged the first ward of pediatric surgery in West Pomerania (in Polish Red Cross hospital). Ten years later he was nominated the head of the Clinic of Pediatric Surgery in the Pomeranian Medical Academy in Szczecin. For many years Prof. Drescher was provincial and regional consultant. He helped to organize a few pediatric surgery wards in Pomerania (Koszalin, Gorzów Wlkp., Słupsk). He died in 1977 in Warsaw. Prof. Drescher published almost 80 scientific papers including two medical books. Traumatology of children and the newborn surgery became his principal area of interest. He was the author of Code of the Ethical and Moral Procedure of the Polish Medical Society. For almost twenty years he was co-author the Annales of Pomeranian Medical Academy. He was a co-founder, next was a president of the Polish Association of

  15. Microsatellites haplotyping of CF chromosomes shows linkage disequilibrium and several founder effects in Brittany (France)

    SciTech Connect

    Raguenes, O.; Ferec, C.; Mercier, B.

    1994-09-01

    A large study on cystic fibrosis (CF) is underway in Brittany (France). It is based on 902 CF patients distributed in 795 families who were or are still followed at the {open_quotes}Centre Helio-Marin{close_quotes} in Roscoff and/or were subjected to a molecular analysis at the {open_quotes}Centre de Biogenetique{close_quotes} in Brest. At present, the CF mutations have been identified in 309 patients born in Brittany, most of them of Celtic origin. A microsatellite (MS) study using IVS 17b TA, IVS 17b CA and IVS 8 CA was also completed in 63 CF patients and their parents (carriers of the {Delta}F508 mutation or the G551D mutation or the 1078delT mutation or the W846X mutation). All the 21 chromosomes carrying the 1078delT mutation had the same MS haplotype (16-21-13), which was also found on 9 of the 83 non-CF chromosomes analyzed. All the 16 chromosomes with the G551D mutation carried another MS haplotype (16-7-17), which was also found on 13.3% of the non-CF chromosomes. All the 6 chromosomes with the W846X mutation carried the 16-32-13 haplotype, also found on 6.0% of the non-CF chromosomes. Sixteen different MS haplotypes were found among the 74 chromosomes carrying the{Delta}F508 mutation, three of them representing 74.3% (55/74) of the chromosomes. These were the 23-31-13 haplotype (31/74 - 41.9%), the 17-31-13 haplotype (11/74 - 14.9%), and the 17-32-13 haplotype (13/74 - 17.6%). These results show that the CF mutations observed in Brittany are in linkage disequilibrium with the MS haplotypes. They also suggest that their presence in Brittany is the consequence of several founder effects.

  16. [Edward Wilhelm Drescher--the founder of pediatric surgery in West Pomerania].

    PubMed

    Pacanowski, J H

    1999-01-01

    Professor Edward Wilhelm Drescher--an eminent Polish pediatric surgeon and pioneer of this specialization in West Pomerania--was born in 1912 in Biłgoraj. His young years he spent in his parents familial town Kalisz, where he attended a very famous college--State Humanistic Grammar-School. In 1937 he graduated from Faculty of Medicine at the Warsaw University. Next year he started his career as a surgeon in the Surgery at Orthopedic Ward of Pediatric Clinic in Warsaw, which was directed by prof. Jan Kossakowski--excellent pediatric surgeon and artist. During the September Campaign he took part in the battle of Bzura and in the defense of Polish capital as the physician in the 25th Regiment of Artillery. In 1940 he joined Polish underground army--AK. In 1944, when the Warsaw Uprising broke out, he was the Commander of the insurgent hospital--Poznańska 11. It was a very well arranged and headed hospital, which admitted about eight hundred wounded soldiers and civilians. After the war for two years he lived in Sopot, where he organized and directed the Surgery Hospital and the Town Outpatients' Department. In 1947 he moved to Szczecin, where he arranged the first ward of pediatric surgery in West Pomerania (in Polish Red Cross hospital). Ten years later he was nominated the head of the Clinic of Pediatric Surgery in the Pomeranian Medical Academy in Szczecin. For many years Prof. Drescher was provincial and regional consultant. He helped to organize a few pediatric surgery wards in Pomerania (Koszalin, Gorzów Wlkp., Słupsk). He died in 1977 in Warsaw. Prof. Drescher published almost 80 scientific papers including two medical books. Traumatology of children and the newborn surgery became his principal area of interest. He was the author of Code of the Ethical and Moral Procedure of the Polish Medical Society. For almost twenty years he was co-author the Annales of Pomeranian Medical Academy. He was a co-founder, next was a president of the Polish Association of

  17. [Professor Adam Nowosławski (1925-2012)--founder of the Polish School of Immunopathology].

    PubMed

    Madaliński, Kazimierz

    2012-01-01

    Professor dr med. Adam Nowosławski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowosławski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowosławski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowosławski received the national medals: Polonia Restituta Crosses

  18. The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos.

    PubMed

    Miyamoto, Kei; Suzuki, Ken-Ichi T; Suzuki, Miyuki; Sakane, Yuto; Sakuma, Tetsushi; Herberg, Sarah; Simeone, Angela; Simpson, David; Jullien, Jerome; Yamamoto, Takashi; Gurdon, J B

    2015-01-01

    Recent advances in genome editing using programmable nucleases have revolutionized gene targeting in various organisms. Successful gene knock-out has been shown in Xenopus, a widely used model organism, although a system enabling less mosaic knock-out in founder embryos (F0) needs to be explored in order to judge phenotypes in the F0 generation. Here, we injected modified highly active transcription activator-like effector nuclease (TALEN) mRNA to oocytes at the germinal vesicle (GV) stage, followed by in vitro maturation and intracytoplasmic sperm injection, to achieve a full knock-out in F0 embryos. Unlike conventional injection methods to fertilized embryos, the injection of TALEN mRNA into GV oocytes allows expression of nucleases before fertilization, enabling them to work from an earlier stage. Using this procedure, most of developed embryos showed full knock-out phenotypes of the pigmentation gene tyrosinase and/or embryonic lethal gene pax6 in the founder generation. In addition, our method permitted a large 1 kb deletion. Thus, we describe nearly complete gene knock-out phenotypes in Xenopus laevis F0 embryos. The presented method will help to accelerate the production of knock-out frogs since we can bypass an extra generation of about 1 year in Xenopus laevis. Meantime, our method provides a unique opportunity to rapidly test the developmental effects of disrupting those genes that do not permit growth to an adult able to reproduce. In addition, the protocol shown here is considerably less invasive than the previously used host transfer since our protocol does not require surgery. The experimental scheme presented is potentially applicable to other organisms such as mammals and fish to resolve common issues of mosaicism in founders.

  19. Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis.

    PubMed

    Bu, Rong; Siraj, Abdul K; Al-Obaisi, Khadija A S; Beg, Shaham; Al Hazmi, Mohsen; Ajarim, Dahish; Tulbah, Asma; Al-Dayel, Fouad; Al-Kuraya, Khawla S

    2016-09-01

    Ethnic differences of breast cancer genomics have prompted us to investigate the spectra of BRCA1 and BRCA2 mutations in different populations. The prevalence and effect of BRCA 1 and BRCA 2 mutations in Middle Eastern population is not fully explored. To characterize the prevalence of BRCA mutations in Middle Eastern breast cancer patients, BRCA mutation screening was performed in 818 unselected breast cancer patients using Capture and/or Sanger sequencing. 19 short tandem repeat (STR) markers were used for founder mutation analysis. In our study, nine different types of deleterious mutation were identified in 28 (3.4%) cases, 25 (89.3%) cases in BRCA 1 and 3 (10.7%) cases in BRCA 2. Seven recurrent mutations identified accounted for 92.9% (26/28) of all the mutant cases. Haplotype analysis was performed to confirm c.1140 dupG and c.4136_4137delCT mutations as novel putative founder mutation, accounting for 46.4% (13/28) of all BRCA mutant cases and 1.6% (13/818) of all the breast cancer cases, respectively. Moreover, BRCA 1 mutation was significantly associated with BRCA 1 protein expression loss (p = 0.0005). Our finding revealed that a substantial number of BRCA mutations were identified in clinically high risk breast cancer from Middle East region. Identification of the mutation spectrum, prevalence and founder effect in Middle Eastern population facilitates genetic counseling, risk assessment and development of cost-effective screening strategy. PMID:27082205

  20. The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos

    PubMed Central

    Suzuki, Miyuki; Sakane, Yuto; Sakuma, Tetsushi; Herberg, Sarah; Simeone, Angela; Simpson, David; Jullien, Jerome; Yamamoto, Takashi; Gurdon, J. B.

    2015-01-01

    Recent advances in genome editing using programmable nucleases have revolutionized gene targeting in various organisms. Successful gene knock-out has been shown in Xenopus, a widely used model organism, although a system enabling less mosaic knock-out in founder embryos (F0) needs to be explored in order to judge phenotypes in the F0 generation. Here, we injected modified highly active transcription activator-like effector nuclease (TALEN) mRNA to oocytes at the germinal vesicle (GV) stage, followed by in vitro maturation and intracytoplasmic sperm injection, to achieve a full knock-out in F0 embryos. Unlike conventional injection methods to fertilized embryos, the injection of TALEN mRNA into GV oocytes allows expression of nucleases before fertilization, enabling them to work from an earlier stage. Using this procedure, most of developed embryos showed full knock-out phenotypes of the pigmentation gene tyrosinase and/or embryonic lethal gene pax6 in the founder generation. In addition, our method permitted a large 1 kb deletion. Thus, we describe nearly complete gene knock-out phenotypes in Xenopus laevis F0 embryos. The presented method will help to accelerate the production of knock-out frogs since we can bypass an extra generation of about 1 year in Xenopus laevis. Meantime, our method provides a unique opportunity to rapidly test the developmental effects of disrupting those genes that do not permit growth to an adult able to reproduce. In addition, the protocol shown here is considerably less invasive than the previously used host transfer since our protocol does not require surgery. The experimental scheme presented is potentially applicable to other organisms such as mammals and fish to resolve common issues of mosaicism in founders. PMID:26580070

  1. Evidence of a founder effect for four cathepsin C gene mutations in Papillon-Lefèvre syndrome patients.

    PubMed

    Zhang, Y; Lundgren, T; Renvert, S; Tatakis, D N; Firatli, E; Uygur, C; Hart, P S; Gorry, M C; Marks, J J; Hart, T C

    2001-02-01

    We describe a mutation and haplotype analysis of Papillon-Lefèvre syndrome probands that provides evidence of a founder effect for four separate cathepsin C mutations. A total of 25 different cathepsin C mutations have been reported in 32 families with Papillon-Lefèvre syndrome (PLS) and associated conditions. A characteristic of these findings is the diversity of different cathepsin C mutations that have been identified. To evaluate the generality of cathepsin C mutations, PLS probands representative of five reportedly unrelated Saudi Arabian families were evaluated by mutational and haplotype analyses. Sequence analysis identified two cathepsin C gene mutations: a novel exon 7 G300D mutation was found in the proband from one family, while probands from four families shared a common R272P mutation in exon 6. The R272P mutation has been previously reported in two other non-Saudi families. The presence of the R272P mutation in probands from these four Saudi families makes this the most frequently reported cathepsin C mutation. To distinguish between the presence of a possible founder effect or a mutational hot spot for the R272P mutation, we performed haplotype analysis using six novel DNA polymorphisms that span a 165 kb interval containing the cathepsin C gene. Results of haplotype analysis for genetic polymorphisms within and flanking the cathepsin C gene are consistent with inheritance of the R272P mutation "identical by descent" from a common ancestor in these four Saudi families. Haplotype analysis of multiple PLS probands homozygous for other cathepsin C mutations (W249X, Q286X, and T153I) also supports inheritance of each of these mutations from common ancestors. These data suggest that four of the more frequently reported cathepsin C mutations have been inherited from common ancestors and provide the first direct evidence for a founder effect for cathepsin C gene mutations in PLS. Identification of these six short tandem repeat polymorphisms that span the

  2. The Unseen Founders Of Quaternary Science - The Men Of Glasgow, Scotland (Invited)

    NASA Astrophysics Data System (ADS)

    Rose, J.

    2010-12-01

    Louis Agassiz (1807-1873) and Charles Lyell (1797-1875) are widely regarded as the founders of Quaternary Science, and there is no doubt that they played their part: Agassiz in 1840 presented and promoted his case for the wide-scale fluctuations of glaciers, and Lyell, through his books and contacts, did much to introduce the subject which we now know as climate change. However there are a number of individuals who contributed to the founding of Quaternary Science who are not so readily recognised and a remarkable fact is that a significant proportion were men without academic training or background who come from, or worked in Glasgow or the adjacent region of central Scotland. First amongst the Glaswegians was James Smith (1782-1867) who, in 1836 presented a paper to the Geological Society of London (where it was duly ignored) in which he suggested, on the basis of fossils dredged from the bed of the Clyde and experience of sailing around Iceland, that the climate of Scotland had been as cold as that of Iceland in the recent past. In 1841, Charles Maclaren (1782-1866) a journalist from Edinburgh, but using information based on raised shorelines near Glasgow proposed what we now know as the glacio-eustatic theory in which the variations in glacier extent control the level of the sea. Perhaps the most important of all was James Croll (1821- 1890) who worked on the theory of ice ages, based on orbital forcing, while janitor at the Andersonian Institute and Museum in Glasgow between 1859-1867. This work was the true precursor to the Milankovitch theory which provides the explanation for the major predictable elements of climate change. Robert Jack (1845-1921) from Irvine, southwest of Glasgow, while doing fieldwork for the British Geological Survey near Loch Lomond close to Glasgow, described in 1874 evidence for non-glacial conditions between tills and clearly recognised that climate could change from glacial to temperate and then glacial climate, before returning to

  3. Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy.

    PubMed

    Landsverk, Megan L; Ruzzo, Elizabeth K; Mefford, Heather C; Buysse, Karen; Buchan, Jillian G; Eichler, Evan E; Petty, Elizabeth M; Peterson, Esther A; Knutzen, Dana M; Barnett, Karen; Farlow, Martin R; Caress, Judy; Parry, Gareth J; Quan, Dianna; Gardner, Kathy L; Hong, Ming; Simmons, Zachary; Bird, Thomas D; Chance, Phillip F; Hannibal, Mark C

    2009-04-01

    Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.

  4. A Population-Based Study of Autosomal-Recessive Disease-Causing Mutations in a Founder Population

    PubMed Central

    Chong, Jessica X.; Ouwenga, Rebecca; Anderson, Rebecca L.; Waggoner, Darrel J.; Ober, Carole

    2012-01-01

    The decreasing cost of whole-genome and whole-exome sequencing has resulted in a renaissance for identifying Mendelian disease mutations, and for the first time it is possible to survey the distribution and characteristics of these mutations in large population samples. We conducted carrier screening for all autosomal-recessive (AR) mutations known to be present in members of a founder population and revealed surprisingly high carrier frequencies for many of these mutations. By utilizing the rich demographic, genetic, and phenotypic data available on these subjects and simulations in the exact pedigree that these individuals belong to, we show that the majority of mutations were most likely introduced into the population by a single founder and then drifted to the high carrier frequencies observed. We further show that although there is an increased incidence of AR diseases overall, the mean carrier burden is likely to be lower in the Hutterites than in the general population. Finally, on the basis of simulations, we predict the presence of 30 or more undiscovered recessive mutations among these subjects, and this would at least double the number of AR diseases that have been reported in this isolated population. PMID:22981120

  5. Megalencephalic leukoencephalopathy with cysts in twelve Egyptian patients: novel mutations in MLC1 and HEPACAM and a founder effect.

    PubMed

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Ismail, Samira I; Hosny, Heba; Omar, Tarek; Effat, Laila; Aglan, Mona S; Temtamy, Samia A; Zaki, Maha S

    2016-10-01

    Two genes causing megalencephalic leukoencephalopathy with subcortical cysts (MLC) have been discovered so far. Here, we identified MLC1 and HEPACAM mutations in ten and two patients, respectively. The molecular results included an unreported inframe duplication mutation (c.929_930dupCTGCTG; p.L309dup) of MLC1 and a novel missense mutation c.293G>A (p.R98H) of HEPACAM. Further, the previously reported missense (c.278C>T; p.S93L) and the deletion/insertion (c.908_918delinsGCA; p.V303Gfs*96) were found in one and 8 patients (75 %), respectively. The 8 patients carrying the p.V303Gfs*96 shared a similar haplotype suggesting a founder effect. All mutations were in the homozygous state proving the autosomal recessive mode of inheritance. The core phenotype of macrocephaly, subcortical cysts and white matter appeared homogeneous although the patients differed in the onset, clinical course, disease severity and brain imaging findings. Our study expands the spectrum of mutations in MLC1 and HEPACAM and supports the genetic and clinical heterogeneity. Further, It confirms c.908_918delinsGCA (p.V303Gfs*96) as a founder mutation among Egyptian patients. This finding will contribute to provide targeted testing for this mutation in MLC patients in our population. PMID:27389245

  6. Founder-cell-specific transcription of the DORNRÖSCHEN-LIKE promoter and integration of the auxin response.

    PubMed

    Comelli, Petra; Glowa, Dorothea; Chandler, John W; Werr, Wolfgang

    2016-01-01

    Transcription of the DORNRÖSCHEN (DRNL) promoter marks lateral-organ founder cells throughout Arabidopsis development, from cotyledons to flowers or floral organs. In the inflorescence apex, DRNL::GFP depicts incipient floral phyllotaxy, and organs in the four floral whorls are differentially prepatterned: the sepals unidirectionally along an abaxial-adaxial axis, the four petals and two lateral stamens in two putative morphogenetic fields, and the medial stamens subsequently in a ring-shaped domain, before two groups of carpel founder cells are specified. The dynamic DRNL transcription pattern is controlled by three enhancer elements, which redundantly and synergistically control qualitative or quantitative aspects of expression, and differentially integrate the auxin response in Arabidopsis inflorescence and floral meristems. The high sequence conservation of all three enhancer elements among the Brassicaceae is striking, which suggests that densely packed cis-regulatory elements are conserved to recruit multiple transcription factors, including auxin response factors, into higher-order enhanceosome complexes. The spatial organization of the enhancers is also conserved, by a microsynteny that extends beyond the Brassicaceae, which relates to enhancer sharing, as the distal element En1 bidirectionally serves DRNL and the upstream At1g24600 gene; the genes are transcribed in opposite directions and possibly comprise a conserved functional chromatin domain.

  7. A Founder Large Deletion Mutation in Xeroderma Pigmentosum-Variant Form in Tunisia: Implication for Molecular Diagnosis and Therapy

    PubMed Central

    Ben Rekaya, Mariem; Laroussi, Nadia; Messaoud, Olfa; Jones, Mariem; Jerbi, Manel; Bouyacoub, Yosra; Chargui, Mariem; Kefi, Rym; Fazaa, Becima; Boubaker, Mohamed Samir; Boussen, Hamouda; Mokni, Mourad; Abdelhak, Sonia; Zghal, Mohamed; Khaled, Aida; Yacoub-Youssef, Houda

    2014-01-01

    Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutation POLH NG_009252.1: g.36847_40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa. PMID:24877075

  8. Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma.

    PubMed

    Ober, C; Cox, N J; Abney, M; Di Rienzo, A; Lander, E S; Changyaleket, B; Gidley, H; Kurtz, B; Lee, J; Nance, M; Pettersson, A; Prescott, J; Richardson, A; Schlenker, E; Summerhill, E; Willadsen, S; Parry, R

    1998-09-01

    Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population. PMID:9700192

  9. Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.

    PubMed

    Chaves, R G; Pereira, L da Veiga; de Araújo, F T; Rozenberg, R; Carvalho, M D F; Coelho, J C; Michelin-Tirelli, K; Chaves, M de Freitas; Cavalcanti, G B

    2015-10-01

    Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation. PMID:25287185

  10. Genetic structure and parasitization-related ability divergence of a nematode fungal pathogen Hirsutella minnesotensis following founder effect in China.

    PubMed

    Shu, Chi; Jiang, Xianzhi; Cheng, Xiaoli; Wang, Niuniu; Chen, Senyu; Xiang, Meichun; Liu, Xingzhong

    2015-08-01

    The fungal parasitoid, Hirsutella minnesotensis, is a dominant parasitoid of the soybean cyst nematode, which is a destruction pest of soybean crops. We investigated population structure and parasitism pattern in samples of H. minnesotensis in China to reveal the spreading pattern of this fungal species and the underlying mechanism generating the parasitization-related ability variability in Chinese population. In cross-inoculation experiments using different combinations of H. minnesotensis and soybean cyst nematode samples from China, most H. minnesotensis isolates fitted the criterion for "local versus foreign" parasitism profile, exhibiting local adaptation pattern to the SCN host. However, the genetic analysis of the single nucleotide polymorphisms with clone-corrected samples based on ten DNA fragments in 56 isolates of H. minnesotensis from China revealed that the Chinese H. minnesotensis population was a clonal lineage that underwent a founder event. The results demonstrated that the Chinese H. minnesotensis population had generated parasitization-related ability diversity after a founder event through individual variation or phenotypic plasticity other than local adaptation. The rapid divergence of parasitization-related abilities with simple genetic structure in Chinese H. minnesotensis population indicates a fundamental potential for the establishment of invasive fungal species, which is a prerequisite for biological control agents.

  11. Transmitted/Founder Simian Immunodeficiency Virus Envelope Sequences in Vesicular Stomatitis and Semliki Forest Virus Vector Immunized Rhesus Macaques

    PubMed Central

    Gambhira, Ratish; Keele, Brandon F.; Schell, John B.; Hunter, Meredith J.; Dufour, Jason P.; Montefiori, David C.; Tang, Haili; Rose, John K.; Rose, Nina; Marx, Preston A.

    2014-01-01

    Identification of transmitted/founder simian immunodeficiency virus (SIV) envelope sequences responsible for infection may prove critical for understanding HIV/SIV mucosal transmission. We used single genome amplification and phylogenetic analyses to characterize transmitted/founder SIVs both in the inoculum and in immunized-infected rhesus monkeys. Single genome amplification of the SIVsmE660 inoculum revealed a maximum diversity of 1.4%. We also noted that the consensus sequence of the challenge stock differed from the vaccine construct in 10 amino acids including 3 changes in the V4 loop. Viral env was prepared from rhesus plasma in 3 groups of 6 immunized with vesicular stomatitis virus (VSV) vectors and boosted with Semliki forest virus (SFV) replicons expressing (a) SIVsmE660 gag-env (b) SIVsmE660 gag-env plus rhesus GM-CSF and (c) control influenza hemagglutinin protein. Macaques were immunized twice with VSV-vectors and once with SFV vector and challenged intrarectally with 4000 TCID50. Single genome amplification characterized the infections of 2 unprotected animals in the gag-env immunized group, both of which had reduced acute plasma viral loads that ended as transient infections indicating partial immune control. Four of 6 rhesus were infected in the gag-env + GM-CSF group which demonstrated that GM-CSF abrogated protection. All 6 animals from the control group were infected having high plasma viral loads. We obtained 246 full-length envelope sequences from SIVsmE660 infected macaques at the peak of infection and determined the number of transmitted/founder variants per animal. Our analysis found that 2 of 2 gag-env vaccinated but infected macaques exhibited single but distinct virus envelope lineages whereas rhesus vaccinated with gag-env-GM-CSF or HA control exhibited both single and multiple env lineages. Because there were only 2 infected animals in the gag-env vaccinated rhesus compared to 10 infected rhesus in the other 2 groups, the significance

  12. Transmitted/founder simian immunodeficiency virus envelope sequences in vesicular stomatitis and Semliki forest virus vector immunized rhesus macaques.

    PubMed

    Gambhira, Ratish; Keele, Brandon F; Schell, John B; Hunter, Meredith J; Dufour, Jason P; Montefiori, David C; Tang, Haili; Rose, John K; Rose, Nina; Marx, Preston A

    2014-01-01

    Identification of transmitted/founder simian immunodeficiency virus (SIV) envelope sequences responsible for infection may prove critical for understanding HIV/SIV mucosal transmission. We used single genome amplification and phylogenetic analyses to characterize transmitted/founder SIVs both in the inoculum and in immunized-infected rhesus monkeys. Single genome amplification of the SIVsmE660 inoculum revealed a maximum diversity of 1.4%. We also noted that the consensus sequence of the challenge stock differed from the vaccine construct in 10 amino acids including 3 changes in the V4 loop. Viral env was prepared from rhesus plasma in 3 groups of 6 immunized with vesicular stomatitis virus (VSV) vectors and boosted with Semliki forest virus (SFV) replicons expressing (a) SIVsmE660 gag-env (b) SIVsmE660 gag-env plus rhesus GM-CSF and (c) control influenza hemagglutinin protein. Macaques were immunized twice with VSV-vectors and once with SFV vector and challenged intrarectally with 4000 TCID50. Single genome amplification characterized the infections of 2 unprotected animals in the gag-env immunized group, both of which had reduced acute plasma viral loads that ended as transient infections indicating partial immune control. Four of 6 rhesus were infected in the gag-env + GM-CSF group which demonstrated that GM-CSF abrogated protection. All 6 animals from the control group were infected having high plasma viral loads. We obtained 246 full-length envelope sequences from SIVsmE660 infected macaques at the peak of infection and determined the number of transmitted/founder variants per animal. Our analysis found that 2 of 2 gag-env vaccinated but infected macaques exhibited single but distinct virus envelope lineages whereas rhesus vaccinated with gag-env-GM-CSF or HA control exhibited both single and multiple env lineages. Because there were only 2 infected animals in the gag-env vaccinated rhesus compared to 10 infected rhesus in the other 2 groups, the significance

  13. ["The blessed Leon Szancer Scholarships Foundation for Poor Students of the Jagiellonian Academy Faculty of Medicine" and its founder].

    PubMed

    Sliz, Małgorzata

    2004-01-01

    The paper is devoted to a small but significant episode in the history of the 19th century philanthropy. It describes one of numerous scholarship foundations existing then and a person of its founder, Leon Szancer (1802-1879). The Szancer's Foundation was created for students of medicine of the Jagiellonian University and 25 persons used its help. Szancer himself was a representative of Poles of Mosaic religion. He had graduated from the Jagiellonian University and afterwards he worked as physician in the Army of the Congress Kingdom of Poland. He participated in the Polish November Insurrection and after its fall he emigrated. He was working in Opatów for many years and spent his last years of life in Krakow.

  14. The history of the German Cardiac Society and the American College of Cardiology and their two founders.

    PubMed

    Lüderitz, Berndt; Holmes, David R; Harold, John

    2013-02-26

    The German Cardiac Society is the oldest national cardiac society in Europe, founded on June 3, 1927, in Bad Nauheim by Dr. Bruno Kisch and Professor Arthur Weber. They were actively supported by Dr. Franz Groedel, who together with Kisch became co-founders of the American College of Cardiology in 1949. Both Groedel and Kisch would be proud to see the fulfillment of their visions and dreams, which was commemorated at the joint session of the two societies held during the 78th annual meeting of the German Cardiac Society in Mannheim, Germany. "It is ironic that their dreadful years in Germany and their loss to German Cardiology helped to contribute to advances in American and international Cardiology," said Dr. Simon Dack, American College of Cardiology president in 1956 and 1957. The legacy of Groedel might be reflected by his own words: "We will meet the future not merely by dreams but by concerned action and inextinguishable enthusiasm". PMID:23428213

  15. Mitochondrial Genome Diversity of Native Americans Supports a Single Early Entry of Founder Populations into America

    PubMed Central

    Silva Jr., Wilson A.; Bonatto, Sandro L.; Holanda, Adriano J.; Ribeiro-dos-Santos, Andrea K.; Paixão, Beatriz M.; Goldman, Gustavo H.; Abe-Sandes, Kiyoko; Rodriguez-Delfin, Luis; Barbosa, Marcela; Paçó-Larson, Maria Luiza; Petzl-Erler, Maria Luiza; Valente, Valeria; Santos, Sidney E. B.; Zago, Marco A.

    2002-01-01

    There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions. However, the small number of nucleotides studied and the nonclocklike rate of mtDNA control-region evolution impose several limitations to these results. Here we provide the sequence analysis of a continuous region of 8.8 kb of the mtDNA outside the D-loop for 40 individuals, 30 of whom are Native Americans whose mtDNA belongs to the four founder haplogroups. Haplogroups A, B, and C form monophyletic clades, but the five haplogroup D sequences have unstable positions and usually do not group together. The high degree of similarity in the nucleotide diversity and time of differentiation (i.e., ∼21,000 years before present) of these four haplogroups support a common origin for these sequences and suggest that the populations who harbor them may also have a common history. Additional evidence supports the idea that this age of differentiation coincides with the process of colonization of the New World and supports the hypothesis of a single and early entry of the ancestral Asian population into the Americas. PMID:12022039

  16. Founder effects and stochastic dispersal at the continental scale of the fungal pathogen of bananas Mycosphaerella fijiensis.

    PubMed

    Rivas, Gonzalo-Galileo; Zapater, Marie-Françoise; Abadie, Catherine; Carlier, Jean

    2004-02-01

    The worldwide destructive epidemic of the fungus Mycosphaerella fijiensis on banana started recently, spreading from South-East Asia. The founder effects detected in the global population structure of M. fijiensis reflected rare migration events among continents through movements of infected plant material. The main objective of this work was to infer gene flow and dispersal processes of M. fijiensis at the continental scale from population structure analysis in recently invaded regions. Samples of isolates were collected from banana plantations in 13 countries in Latin America and the Caribbean and in Africa. The isolates were analysed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and microsatellite molecular markers. The results indicate that a high level of genetic diversity was maintained at the plantation and the plant scales. The loci were at gametic equilibrium in most of the samples analysed, supporting the hypothesis of the existence of random-mating populations of M. fijiensis, even at the plant scale. A low level of gene diversity was observed in some populations from the Africa and Latin America-Caribbean regions. Nearly half the populations analysed showed a significant deviation from mutation-drift equilibrium with gene diversity excess. Finally, a high level of genetic differentiation was detected between populations from Africa (FST = 0.19) and from the Latin America-Caribbean region (FST = 0.30). These results show that founder effects accompanied the recent invasion of M. fijiensis in both regions, suggesting stochastic spread of the disease at the continental scale. This spread might be caused by either the limited dispersal of ascospores or by movements of infected plant material.

  17. The CHEK2 del5395 is a founder mutation without direct effects for cancer risk in the latvian population

    PubMed Central

    Kalniete, D; Nakazawa-Miklasevica, M; Irmejs, A; Vjaters, E; Gardovskis, J; Miklasevics, E

    2015-01-01

    Abstract Our objective was to determine: 1) whether the checkpoint kinase 2 (CHEK2) del5395 (g.27417113-27422508 del, NC_000022.11) is a founder mutation in the Latvian population, 2) if there is an association between CHEK2 del5395 mutation and cancer risk, and 3) and whether the CHEK2 del5395 mutation impacts cancer predisposition in Chernobyl disaster liquidators (the civil and military personnel who were called upon to deal with consequences of the 1986 nuclear disaster) as well as geriatric populations. We recruited 438 breast cancer patients, 568 colorectal cancer patients, 399 ovarian cancer patients, 419 prostate cancer patients, 526 healthy blood donors, 480 Chernobyl disaster liquidators and 444 geriatric cancer-free participants. DNA samples were isolated from blood samples and subjected to multiplex polymerase chain reaction (PCR). The truncation of del5395 was estimated by fragment size of the multiplex PCR.All groups were compared to the healthy blood donors using Fisher’s exact test. All p values were two-sided and the odds ratios (OR) calculated by two-by-two table. In cancer groups, the del5395 mutation was most frequently observed in the ovarian cancer group (1.00%, OR = 1.32). In control groups, the del5395 mutation was most frequent (0.76%) in the healthy donors, which exceeded its frequency in the Chernobyl liquidators group and the geriatric group by 0.01 and 0.08%, respectively. For all groups, the OR appeared to be >1 only in ovarian cancer patients. However, OR rates showed no statistical significance in either cancer or control groups, with the p value fluctuating within the range of 0.39-1.00. The CHEK2 gene del5395 is a founder mutation in the Latvian population, which, however, does not have a direct impact on genetic predisposition toward colorectal, breast, ovarian and prostate cancer. PMID:27785394

  18. HealthSouth's most wanted. Founder and former chairman and CEO Richard Scrushy is indicted for 85 counts of conspiracy, fraud and money laundering.

    PubMed

    Piotrowski, Julie

    2003-11-10

    Wake-up call for the industry or an isolated case of corporate chicanery? Healthcare experts are divided on the import of Richard Scrushy's indictment on 85 counts last week in connection with the financial scandal at HealthSouth Corp. The indictment alleges the company founder relied on electronic and telephone surveillance, threats and intimidation to control his accomplices.

  19. HealthSouth's most wanted. Founder and former chairman and CEO Richard Scrushy is indicted for 85 counts of conspiracy, fraud and money laundering.

    PubMed

    Piotrowski, Julie

    2003-11-10

    Wake-up call for the industry or an isolated case of corporate chicanery? Healthcare experts are divided on the import of Richard Scrushy's indictment on 85 counts last week in connection with the financial scandal at HealthSouth Corp. The indictment alleges the company founder relied on electronic and telephone surveillance, threats and intimidation to control his accomplices. PMID:14666542

  20. 500th birthday of Andreas Vesalius, the founder of modern anatomy: "vivitur ingenio, caetera mortis erunt" ("genius lives on, all else is mortal").

    PubMed

    Hadzic, Admir; Sadeghi, Neda; Vandepitte, Catherine; Vandepitte, Walter; Van de Velde, Marc; Hadzic, Alen; Van Robays, Johan; Heylen, Rene; Herijgers, Paul; Vloka, Caroline; Van Zundert, Jan

    2014-01-01

    It is often said that regional anesthesia is the practice of applied anatomy. Therefore, it is fitting that on the occasion of his 500th birthday, we celebrate the life and work of the brilliant Flemish anatomist, Andreas Vesalius (1514-1564), the founder of modern anatomy. PMID:25340483

  1. A Bundle of Silences: Examining the Racial Representation of Black Founding Fathers of the United States through Glenn Beck's "Founders' Fridays"

    ERIC Educational Resources Information Center

    King, LaGarrett J.; Womac, Patrick

    2014-01-01

    This article explores the discourse on Black Founding Fathers through Glenn Beck's television show, "Founders' Fridays". According to Beck, this 2010 summer television special was an opportunity to present Black American history in a more nuanced and truthful way. The theoretical framework, silencing the past, is used to…

  2. Patterns of genetic diversity reveal multiple introductions and recurrent founder effects during range expansion in invasive populations of Geranium carolinianum (Geraniaceae).

    PubMed

    Shirk, R Y; Hamrick, J L; Zhang, C; Qiang, S

    2014-05-01

    Genetic diversity, and thus the adaptive potential of invasive populations, is largely based on three factors: patterns of genetic diversity in the species' native range, the number and location of introductions and the number of founding individuals per introduction. Specifically, reductions in genetic diversity ('founder effects') should be stronger for species with low within-population diversity in their native range and few introductions of few individuals to the invasive range. We test these predictions with Geranium carolinianum, a winter annual herb native to North America and invasive in China. We measure the extent of founder effects using allozymes and microsatellites, and ask whether this is consistent with its colonization history and patterns of diversity in the native range. In the native range, genetic diversity is higher and structure is lower than expected based on life history traits. In China, our results provide evidence for multiple introductions near Nanjing, Jiangsu province, with subsequent range expansion to the west and south. Patterns of genetic diversity across China reveal weak founder effects that are driven largely by low-diversity populations at the expansion front, away from the introduction location. This suggests that reduced diversity in China has resulted from successive founder events during range expansion, and that the loss of genetic diversity in the Nanjing area was mitigated by multiple introductions from diverse source populations. This has implications for the future of G. carolinianum in China, as continued gene flow among populations should eventually increase genetic diversity within the more recently founded populations.

  3. The Struggle for Community and Respectability: Black Women School Founders and the Politics of Character Education in the Early Twentieth Century

    ERIC Educational Resources Information Center

    Bair, Sarah D.

    2009-01-01

    The author examines character education within the context of early twentieth-century, Black schooling and discusses how school founders, Mary McLeod Bethune, Nannie Helen Burroughs, and Charlotte Hawkins Brown, used the language and practice of character education to help their students confront racism and navigate a segregated society. These…

  4. 500th birthday of Andreas Vesalius, the founder of modern anatomy: "vivitur ingenio, caetera mortis erunt" ("genius lives on, all else is mortal").

    PubMed

    Hadzic, Admir; Sadeghi, Neda; Vandepitte, Catherine; Vandepitte, Walter; Van de Velde, Marc; Hadzic, Alen; Van Robays, Johan; Heylen, Rene; Herijgers, Paul; Vloka, Caroline; Van Zundert, Jan

    2014-01-01

    It is often said that regional anesthesia is the practice of applied anatomy. Therefore, it is fitting that on the occasion of his 500th birthday, we celebrate the life and work of the brilliant Flemish anatomist, Andreas Vesalius (1514-1564), the founder of modern anatomy.

  5. Investigation of CYP21A2 mutations in Turkish patients with 21-hydroxylase deficiency and a novel founder mutation.

    PubMed

    Toraman, Bayram; Ökten, Ayşenur; Kalay, Ersan; Karagüzel, Gülay; Dinçer, Tuba; Açıkgöz, Emel Gül; Karagüzel, Ahmet

    2013-01-15

    Congenital adrenal hyperplasia (CAH) is a group of autosomal recessively inherited disorders characterized by impaired production of adrenal steroids. Approximately 95% of all CAH are caused by mutations of the CYP21A2 that encodes 21-hydroxylase. In this study, mutation analyses of CYP21A2 were performed in 48 CAH patients from 45 Turkish families with the clinical diagnosis of 21-hydroxylase deficiency (21OHD). While in 39 (86.7%) of 21OHD patients, disease causing CYP21A2 mutations were identified in both alleles, in two 21OHD patients CYP21A2 mutations were identified only in one allele. In four patients, mutation was not detected at all. In total, seventeen known and one novel, disease causing CYP21A2 mutations were observed. Among identified mutations, previously described c.293-13C/A>G, large rearrangements and p.Q319X mutations were the most common mutations accounting for 33.3%, 14.4% and 12.2% of all evaluated chromosomes, respectively. In six families (13.3%) a novel founder mutation, c.2T>C (p.M1?), inactivating the translation initiation codon was found. This mutation is not present in pseudogene CYP21A1P and causes the classical form of the disease in six patients. In addition, depending on the nature of the rearrangements CYP21A1P/CYP21A2 chimeras were further classified as CH(c/d), and CH-1(c) was shown to be the most prominent chimera in our study group. In conclusion, with this study we identified a novel founder CYP21A2 mutation and suggest a further classification for CYP21A1P/CYP21A2 chimeras depending on the combination of junction site position and whether it is occurred as a result of deletion or conversion. Absence of disease causing mutation of CYP21A2 in ten of screened ninety chromosomes suggests the contribution of regulatory elements in occurrences of CAH due to the 21OHD.

  6. Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations

    PubMed Central

    Banin, Eyal

    2015-01-01

    Purpose Nonsyndromic retinitis pigmentosa (RP) is the most common inherited retinal degeneration, and prevalence of the disease has been reported in populations of American and European origin with a relatively low consanguinity rate. Our aim was to determine the prevalence of nonsyndromic RP in the Jerusalem region, which has a population of about 1 million individuals with a high rate of consanguinity. Methods The patients’ clinical data included eye exam findings (visual acuity, anterior segment, and funduscopy) as well as electroretinographic (ERG) testing results under scotopic and photopic conditions. Mutation analysis on a subgroup of patients was performed mainly with candidate gene analysis and homozygosity mapping. Results We evaluated the medical records of patients with degenerative retinal diseases residing in the Jerusalem region who were examined over the past 20 years in a large tertiary medical center. A total of 453 individuals affected with nonsyndromic RP were diagnosed at our center, according to funduscopic findings and ERG testing. Based on the estimated population size of 945,000 individuals who reside in the vicinity of Jerusalem, the prevalence of nonsyndromic RP in this region is 1:2,086. The prevalence of RP was higher among Arab Muslims (1:1,798) compared to Jews (1:2,230), mainly due to consanguineous marriages that are more common in the Arab Muslim population. To identify the genetic causes of RP in our cohort, we recruited 383 patients from 183 different families for genetic analysis: 70 with autosomal recessive (AR) inheritance, 15 with autosomal dominant, 86 isolate cases, and 12 with an X-linked inheritance pattern. In 64 (35%) of the families, we identified the genetic cause of the disease, and we revised the inheritance pattern of 20 isolate cases to the AR pattern; 49% of the families in our cohort had AR inheritance. Interestingly, in 42 (66%) of the genetically identified families, the cause of disease was a founder

  7. Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci

    PubMed Central

    Raelson, John V.; Little, Randall D.; Ruether, Andreas; Fournier, Hélène; Paquin, Bruno; Van Eerdewegh, Paul; Bradley, W. E. C.; Croteau, Pascal; Nguyen-Huu, Quynh; Segal, Jonathan; Debrus, Sophie; Allard, René; Rosenstiel, Philip; Franke, Andre; Jacobs, Gunnar; Nikolaus, Susanna; Vidal, Jean-Michel; Szego, Peter; Laplante, Nathalie; Clark, Hilary F.; Paulussen, René J.; Hooper, John W.; Keith, Tim P.; Belouchi, Abdelmajid; Schreiber, Stefan

    2007-01-01

    Genome-wide association (GWA) studies offer a powerful unbiased method for the identification of multiple susceptibility genes for complex diseases. Here we report the results of a GWA study for Crohn's disease (CD) using family trios from the Quebec Founder Population (QFP). Haplotype-based association analyses identified multiple regions associated with the disease that met the criteria for genome-wide significance, with many containing a gene whose function appears relevant to CD. A proportion of these were replicated in two independent German Caucasian samples, including the established CD loci NOD2 and IBD5. The recently described IL23R locus was also identified and replicated. For this region, multiple individuals with all major haplotypes in the QFP were sequenced and extensive fine mapping performed to identify risk and protective alleles. Several additional loci, including a region on 3p21 containing several plausible candidate genes, a region near JAKMIP1 on 4p16.1, and two larger regions on chromosome 17 were replicated. Together with previously published loci, the spectrum of CD genes identified to date involves biochemical networks that affect epithelial defense mechanisms, innate and adaptive immune response, and the repair or remodeling of tissue. PMID:17804789

  8. A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites

    PubMed Central

    Chong, Jessica X; Oktay, A Afşin; Dai, Zunyan; Swoboda, Kathryn J; Prior, Thomas W; Ober, Carole

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive (AR) neuromuscular disease that is one of the most common lethal genetic disorders in children, with carrier frequencies as high as ∼1 in 35 in US Whites. As part of our genetic studies in the Hutterites from South Dakota, we identified a large 22 Mb run of homozygosity, spanning the SMA locus in an affected child, of which 10 Mb was also homozygous in three affected Hutterites from Montana, supporting a single founder origin for the mutation. We developed a haplotype-based method for identifying carriers of the SMN1 deletion that leveraged existing genome-wide SNP genotype data for ∼1400 Hutterites. In combination with two direct PCR-based assays, we identified 176 carriers of the SMN1 deletion, one asymptomatic homozygous adult and three carriers of a de novo deletion. This corresponds to a carrier frequency of one in eight (12.5%) in the South Dakota Hutterites, representing the highest carrier frequency reported to date for SMA and for an AR disease in the Hutterite population. Lastly, we show that 26 SNPs can be used to predict SMA carrier status in the Hutterites, with 99.86% specificity and 99.71% sensitivity. PMID:21610747

  9. Alfred Russel Wallace (1823-1913): the forgotten co-founder of the Neo-Darwinian theory of biological evolution.

    PubMed

    Kutschera, Ulrich; Hossfeld, Uwe

    2013-12-01

    The British naturalist Alfred Russel Wallace (1823-1913), who had to leave school aged 14 and never attended university, did extensive fieldwork, first in the Amazon River basin (1848-1852) and then in Southeast Asia (1854-1862). Based on this experience, and after reading the corresponding scientific literature, Wallace postulated that species were not created, but are modified descendants of pre-existing varieties (Sarawak Law paper, 1855). Evolution is brought about by a struggle for existence via natural selection, which results in the adaptation of those individuals in variable populations who survive and reproduce (Ternate essay, 1858). In his monograph Darwinism (1889), and in subsequent publications, Wallace extended the contents of Darwin's Origin of Species (1859) into the Neo-Darwinian theory of biological evolution, with reference to the work of August Weismann (1834-1914). Wallace also became the (co)-founder of biogeography, biodiversity research, astrobiology and evolutionary anthropology. Moreover, he envisioned what was later called the anthropocene (i.e., the age of human environmental destructiveness). However, since Wallace believed in atheistic spiritualism and mixed up scientific facts and supernatural speculations in some of his writings, he remains a controversial figure in the history of biology. PMID:23982797

  10. The Role of bZIP Transcription Factors in Green Plant Evolution: Adaptive Features Emerging from Four Founder Genes

    PubMed Central

    Schrago, Carlos Guerra; dos Santos, Renato Vicentini; Mueller-Roeber, Bernd; Vincentz, Michel

    2008-01-01

    Background Transcription factors of the basic leucine zipper (bZIP) family control important processes in all eukaryotes. In plants, bZIPs are regulators of many central developmental and physiological processes including photomorphogenesis, leaf and seed formation, energy homeostasis, and abiotic and biotic stress responses. Here we performed a comprehensive phylogenetic analysis of bZIP genes from algae, mosses, ferns, gymnosperms and angiosperms. Methodology/Principal Findings We identified 13 groups of bZIP homologues in angiosperms, three more than known before, that represent 34 Possible Groups of Orthologues (PoGOs). The 34 PoGOs may correspond to the complete set of ancestral angiosperm bZIP genes that participated in the diversification of flowering plants. Homologous genes dedicated to seed-related processes and ABA-mediated stress responses originated in the common ancestor of seed plants, and three groups of homologues emerged in the angiosperm lineage, of which one group plays a role in optimizing the use of energy. Conclusions/Significance Our data suggest that the ancestor of green plants possessed four bZIP genes functionally involved in oxidative stress and unfolded protein responses that are bZIP-mediated processes in all eukaryotes, but also in light-dependent regulations. The four founder genes amplified and diverged significantly, generating traits that benefited the colonization of new environments. PMID:18698409

  11. Four common glomulin mutations cause two thirds of glomuvenous malformations ("familial glomangiomas"): evidence for a founder effect

    PubMed Central

    Brouillard, P; Ghassibe, M; Penington, A; Boon, L; Dompmartin, A; Temple, I; Cordisco, M; Adams, D; Piette, F; Harper, J; Syed, S; Boralevi, F; Taieb, A; Danda, S; Baselga, E; Enjolras, O; Mulliken, J; Vikkula, M

    2005-01-01

    Background: Glomuvenous malformation (GVM) ("familial glomangioma") is a localised cutaneous vascular lesion histologically characterised by abnormal smooth muscle-like "glomus cells" in the walls of distended endothelium lined channels. Inheritable GVM has been linked to chromosome 1p21-22 and is caused by truncating mutations in glomulin. A double hit mutation was identified in one lesion. This finding suggests that GVM results from complete localised loss of function and explains the paradominant mode of inheritance. Objective: To report on the identification of a mutation in glomulin in 23 additional families with GVM. Results: Three mutations are new; the others have been described previously. Among the 17 different inherited mutations in glomulin known up to now in 43 families, the 157delAAGAA mutation is the most common and was present in 21 families (48.8%). Mutation 108C→A was found in five families (11.8%), and the mutations 554delA+556delCCT and 1179delCAA were present together in two families (4.7% each). Polymorphic markers suggested a founder effect for all four mutations. Conclusions: Screening for these mutations should lead to a genetic diagnosis in about 70% of patients with inherited GVM. So far, a mutation in glomulin has been found in all GVM families tested, thus demonstrating locus homogeneity. PMID:15689436

  12. Localization of the familial Mediterranean fever gene (FMF) to a 250-kb interval in non-Ashkenazi Jewish founder haplotypes

    SciTech Connect

    1996-09-01

    Chromosome 16p13.3 harbors a gene (MEF) associated with familial Mediterranean fever (FMF), a recessive disease very common in populations of Mediterranean ancestry. In the course of positional cloning of MEF, we genotyped 26 non-Ashkenazi Jewish FMF pedigrees (310 meioses) with 15 microsatellite markers, most of which were recently developed by Genethon. Identification of recombination events in the haplotypes allowed narrowing of the MEF interval to a region between D16S3124 (telomeric) and D16S475 (centromeric). Two markers, D16S3070 and D16S3275, a microsatellite marker isolated from a YAC that also contains D16S3070, showed no recombination with the disease. Linkage disequilibrium and haplotype analysis high-lighted the existence of a founder haplotype in our population. The core ancestral alleles were present in 71% of MEF-bearing chromosomes at loci D16S3070 and D16S3275. Furthermore, identification of historical crossing-over events in these pedigrees indicated that MEF is located between these two loci, which are both contained in a 250-kb genomic fragment. 24 refs., 4 figs., 3 tabs.

  13. Alfred Russel Wallace (1823-1913): the forgotten co-founder of the Neo-Darwinian theory of biological evolution.

    PubMed

    Kutschera, Ulrich; Hossfeld, Uwe

    2013-12-01

    The British naturalist Alfred Russel Wallace (1823-1913), who had to leave school aged 14 and never attended university, did extensive fieldwork, first in the Amazon River basin (1848-1852) and then in Southeast Asia (1854-1862). Based on this experience, and after reading the corresponding scientific literature, Wallace postulated that species were not created, but are modified descendants of pre-existing varieties (Sarawak Law paper, 1855). Evolution is brought about by a struggle for existence via natural selection, which results in the adaptation of those individuals in variable populations who survive and reproduce (Ternate essay, 1858). In his monograph Darwinism (1889), and in subsequent publications, Wallace extended the contents of Darwin's Origin of Species (1859) into the Neo-Darwinian theory of biological evolution, with reference to the work of August Weismann (1834-1914). Wallace also became the (co)-founder of biogeography, biodiversity research, astrobiology and evolutionary anthropology. Moreover, he envisioned what was later called the anthropocene (i.e., the age of human environmental destructiveness). However, since Wallace believed in atheistic spiritualism and mixed up scientific facts and supernatural speculations in some of his writings, he remains a controversial figure in the history of biology.

  14. [Detection of a clonal complex with Brucella abortus biovar 2 genotype as founder in B. abortus isolates from Argentina].

    PubMed

    Hollender, Daiana; Conde, Sandra B; Salustio, Eduardo; Samartino, Luis E

    2013-01-01

    Brucella abortus is the causative agent of bovine brucellosis, a worldwide zoonosis. Up to date, eight biovars of B. abortus have been described. In Argentina, biovar 1 is the most frequently isolated. However, biovar 2, which is more pathogenic than biovar 1, is also found. Molecular methods for subtyping isolates are necessary for allowing epidemiological surveillance and control of eradication programs. Due to the genetic homogeneity of the genus Brucella, the development of molecular typing tools has been difficult. The publication of microorganism genomes facilitates the design of this approach. The aim of this work was to employ a Multiple Locus VNTR Analysis (MLVA) scheme for strains from Argentina isolated in our laboratory. From the 56 isolates analyzed, 47 different genotypic profiles were obtained. All the strains typed as biovar 2 showed the same profile. This scheme allowed assigning each isolate to the biovar it belongs to. All the genotypes were related using the goeBURST analysis and biovar 2 was proposed as founder.

  15. Phenylalanine hydroxylase deficiency in Mexico: genotype-phenotype correlations, BH4 responsiveness and evidence of a founder effect.

    PubMed

    Vela-Amieva, M; Abreu-González, M; González-del Angel, A; Ibarra-González, I; Fernández-Lainez, C; Barrientos-Ríos, R; Monroy-Santoyo, S; Guillén-López, S; Alcántara-Ortigoza, M A

    2015-07-01

    The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is unknown, although it has been suggested that PKU variants could have a differential geographical distribution. Genotype-phenotype correlations and genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4 ) have never been performed. We sequenced the PAH gene and determined the geographic origin of each allele, mini-haplotype associated, genotype-phenotype correlations and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The mutational spectrum included 34 variants with c.60+5G>T being the most frequent (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype-phenotype correlation was concordant in 70.8%. The genotype-based prediction to BH4 -responsiveness was 41.7%, this information could be useful for the rational selection of candidates for BH4 testing and therapy.

  16. Genetic variation of the Turnip mosaic virus population of Vietnam: a case study of founder, regional and local influences.

    PubMed

    Nguyen, Huy Duc; Tran, Hoa Thi Nhu; Ohshima, Kazusato

    2013-01-01

    Turnip mosaic virus (TuMV) is one of the most important viruses infecting a wide range of plant species, primarily from the family Brassicaceae. Thirty TuMV isolates were collected from Brassica and Raphanus plants in Vietnam during 2006-2008. Host reaction studies showed that many of the isolates belonged to Brassica/Raphanus (BR) host-infecting type. Sequence-based phylogenetic and population genetic analyses were made of the complete polyprotein gene sequences, and of four non-recombinogenic regions of those sequences (i.e. genes of the helper-component proteinase protein, protein 3, nuclear inclusion b protein and coat protein). These were used to assess the subpopulation differentiation and divergence between Vietnamese TuMV populations and those of nearby Asian countries. Nine inter- and intralineage recombination type patterns were identified in the genomes of the Vietnamese isolates, of which seven were novel. All the Vietnamese non-recombinant isolates fell into the world-B group of TuMV and clustered with Chinese isolates. The estimates of genetic differentiation and gene flow reveal that the TuMV populations of Vietnam, China and Japan are genetically linked but have clear local founder effects. This, the first population genetic study of a TuMV population in Southeast Asia, indicates the importance of such studies for providing the scientific basis of control strategies. PMID:23201192

  17. Congenital lamellar ichthyosis in Tunisia is caused by a founder nonsense mutation in the TGM1 gene.

    PubMed

    Louhichi, Nacim; Hadjsalem, Ikhlass; Marrakchi, Slaheddine; Trabelsi, Fatma; Masmoudi, Abderrahmen; Turki, Hamida; Fakhfakh, Faiza

    2013-03-01

    Lamellar ichthyosis (LI, MIM# 242300) is a severe autosomal recessive genodermatosis present at birth in the form of collodion membrane covering the neonate. Mutations in the TGM1 gene encoding transglutaminase-1 are a major cause of LI. In this study molecular analysis of two LI Tunisian patients revealed a common nonsense c.788G>A mutation in TGM1 gene. The identification of a cluster of LI pedigrees carrying the c.788G>A mutation in a specific area raises the question of the origin of this mutation from a common ancestor. We carried out a haplotype-based analysis by way of genotyping 4 microsatellite markers and 8 SNPs flanking and within the TGM1 gene spanning a region of 6 Mb. Haplotype reconstruction from genotypes of all members of the affected pedigrees indicated that all carriers for the mutation c.788G>A harbored the same haplotype, indicating common ancestor. The finding of a founder effect in a rare disease is essential for the genetic diagnosis and the genetic counselling of affected LI pedigrees in Tunisia.

  18. Pyridoxine-dependent epilepsy in Tunisia is caused by a founder missense mutation of the ALDH7A1 gene.

    PubMed

    Tlili, Abdelaziz; Hamida Hentati, Nadia; Chaabane, Rim; Gargouri, Abdellatif; Fakhfakh, Faiza

    2013-04-15

    Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder characterized by seizures and therapeutic response to pharmacological dose of pyridoxine. Mutations in the ALDH7A1 gene, encoding α-aminoadipic semialdehyde (α-AASA) dehydrogenase (antiquitin), have been reported to cause PDE in most patients. In this study molecular analysis of seven PDE Tunisian patients revealed a common missense c.1364T>C mutation in the ALDH7A1 gene. The identification of a cluster of PDE pedigrees carrying the c.1364T>C mutation in a specific area raises the question of the origin of this mutation from a common ancestor. We carried out a genotype-based analysis by way of genotyping a new generated microsatellite marker within the ALDH7A1 gene. Genotype reconstruction of all affected pedigree members indicate that all c.1364T>C mutation carriers harbored the same allele, indicating a common ancestor. The finding of a founder effect in a rare disease is essential for the genetic diagnosis and the genetic counseling of affected PDE pedigrees in Tunisia.

  19. Genetic consequences of a century of protection: serial founder events and survival of the little spotted kiwi (Apteryx owenii)

    PubMed Central

    Ramstad, Kristina M.; Colbourne, Rogan M.; Robertson, Hugh A.; Allendorf, Fred W.; Daugherty, Charles H.

    2013-01-01

    We present the outcome of a century of post-bottleneck isolation of a long-lived species, the little spotted kiwi (Apteryx owenii, LSK) and demonstrate that profound genetic consequences can result from protecting few individuals in isolation. LSK were saved from extinction by translocation of five birds from South Island, New Zealand to Kapiti Island 100 years ago. The Kapiti population now numbers some 1200 birds and provides founders for new populations. We used 15 microsatellite loci to compare genetic variation among Kapiti LSK and the populations of Red Mercury, Tiritiri Matangi and Long Islands that were founded with birds from Kapiti. Two LSK native to D'Urville Island were also placed on Long Island. We found extremely low genetic variation and signatures of acute and recent genetic bottleneck effects in all four populations, indicating that LSK have survived multiple genetic bottlenecks. The Long Island population appears to have arisen from a single mating pair from Kapiti, suggesting there is no genetic contribution from D'Urville birds among extant LSK. The Ne/NC ratio of Kapiti Island LSK (0.03) is exceptionally low for terrestrial vertebrates and suggests that genetic diversity might still be eroding in this population, despite its large census size. PMID:23677342

  20. History of the ISS/SIC: Antoine Depage, one of the founders of the ISS/SIC.

    PubMed

    Van Hee, R

    2002-10-01

    Antoine Depage, born near Brussels in 1862, was one of the founders and first Secretary General of the Société Internationale de Chirurgie (ISS-SIC). After an excellent medical education at the Free Brussels University, he became professor at the same university at the age of 27. Surgically trained by Prof. Thiriar, he became one of the leading Belgian surgeons at the end of the nineteenth century, and he published more than 100 articles in national and international journals. In 1907 he founded a school for nurses in Brussels, to be directed by Edith Cavell. He also vigorously transformed the organization of the public hospitals in the Belgian capital. During World War I Queen Elisabeth appointed him surgeon-in-chief of the Océan-hospital in De Panne, where more than 50,000 soldiers with wounds, fractures, cerebral trauma, nitrous gas intoxication, and infectious diseases, among other problems were treated. The results he and his team obtained were excellent, and mortality was low. Many surgeons, including Alexis Carrel, as well as distinguished political leaders came to visit him in the hospital barracks. After the war he was honored by many political and scientific organizations, including the Société Internationale de Chirurgie. He served our Society not only as Secretary General from 1902 to 1912 but became President of the 4th Congress of the ISS-SIC in New York. Antoine Depage died after a long illness in 1925. PMID:12205562

  1. Concordance of nuclear and mitochondrial DNA markers in detecting a founder event in Lake Clark sockeye salmon

    USGS Publications Warehouse

    Ramstad, Kristina M.; Woody, Carol Ann; Habicht, Chris; Sage, G. Kevin; Seeb, James E.; Allendorf, Fred W.

    2007-01-01

    Genetic bottleneck effects can reduce genetic variation, persistence probability, and evolutionary potential of populations. Previous microsatellite analysis suggested a bottleneck associated with a common founding of sock-eye salmon Oncorhynchus nerka populations of Lake Clark, Alaska, about 100 to 400 generations ago. The common foundingevent occurred after the last glacial recession and resulted in reduced allelic diversity and strong divergence of Lake Clarksockeye salmon relative to neighboring Six Mile Lake and LakeIliamna populations. Here we used two additional genetic marker types (allozymes and mtDNA) to examine these patterns further. Allozyme and mtDNA results were congruent with the microsatellite data in suggesting a common founder event in LakeClark sockeye salmon and confirmed the divergence of Lake Clarkpopulations from neighboring Six Mile Lake and Lake Iliamna populations. The use of multiple marker types provided better understanding of the bottleneck in Lake Clark. For example, the Sucker Bay Lake population had an exceptionally severe reduction in allelic diversity at microsatellite loci, but not at mtDNA. This suggests that the reduced microsatellite variation in Sucker Bay Lake fish is due to consistently smaller effective population size than other Lake Clark populations, rather than a more acute or additional bottleneck since founding. Caution is urged in using reduced heterozygosity as a measure of genetic bottleneck effects because stochastic variance among loci resulted in an overall increase in allozyme heterozygosity within bottlenecked Lake Clark populations. However, heterozygosity excess, which assesses heterozygosity relative to allelic variation, detected genetic bottleneck effects in both allozyme and microsatellite loci. 

  2. Biophysical characterization of M1476I, a sodium channel founder mutation associated with cold-induced myotonia in French Canadians.

    PubMed

    Zhao, Juan; Duprè, Nicolas; Puymirat, Jack; Chahine, Mohamed

    2012-06-01

    M1476I, a French Canadian founder mutation of Na⁺ channel Nav1.4, causes potassium-aggravated myotonia, with cold-induced myotonia as the most distinctive clinical feature. Mexiletine, a class 1B local anaesthetic, relieves the myotonic symptoms of patients carrying the M1476I mutation. We used the patch-clamp method to investigate the functional characteristics of this mutation by heterologous expression in tsA201 cells. The M1476I mutation caused an increased persistent Na⁺ current, a 2- to 3-fold slower fast inactivation, a 6.4 mV depolarizing shift in the midpoint of steady-state inactivation, and an accelerated recovery from fast inactivation compared to the wild-type (WT) channel. Cooling slowed the kinetics of both channel types and increased the amplitude of the persistent current in M1476I channels.Mexiletine suppressed the persistent Na⁺ current generated by the M1476I mutation and blocked both WT and M1476I channels in a use- dependent manner. The inactivation-deficient M1476I channels were less susceptible to mexiletine during repetitive pulses. The decreased use-dependent block of M1476I channels might have resulted from the slower onset of mexiletine block, and/or the faster recovery from mexiletine block, given that the affinity of mexiletine for the inactivated state of the WT and mutant channels was similar. Increased extracellular concentrations of potassium had no effect on either M1476I or WT currents. These results indicated that cooling can augment the disruption of the voltage dependence of fast inactivation by M1476I channels. PMID:22250216

  3. Biophysical characterization of M1476I, a sodium channel founder mutation associated with cold-induced myotonia in French Canadians.

    PubMed

    Zhao, Juan; Duprè, Nicolas; Puymirat, Jack; Chahine, Mohamed

    2012-06-01

    M1476I, a French Canadian founder mutation of Na⁺ channel Nav1.4, causes potassium-aggravated myotonia, with cold-induced myotonia as the most distinctive clinical feature. Mexiletine, a class 1B local anaesthetic, relieves the myotonic symptoms of patients carrying the M1476I mutation. We used the patch-clamp method to investigate the functional characteristics of this mutation by heterologous expression in tsA201 cells. The M1476I mutation caused an increased persistent Na⁺ current, a 2- to 3-fold slower fast inactivation, a 6.4 mV depolarizing shift in the midpoint of steady-state inactivation, and an accelerated recovery from fast inactivation compared to the wild-type (WT) channel. Cooling slowed the kinetics of both channel types and increased the amplitude of the persistent current in M1476I channels.Mexiletine suppressed the persistent Na⁺ current generated by the M1476I mutation and blocked both WT and M1476I channels in a use- dependent manner. The inactivation-deficient M1476I channels were less susceptible to mexiletine during repetitive pulses. The decreased use-dependent block of M1476I channels might have resulted from the slower onset of mexiletine block, and/or the faster recovery from mexiletine block, given that the affinity of mexiletine for the inactivated state of the WT and mutant channels was similar. Increased extracellular concentrations of potassium had no effect on either M1476I or WT currents. These results indicated that cooling can augment the disruption of the voltage dependence of fast inactivation by M1476I channels.

  4. Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption.

    PubMed

    Rothenberger, Meghan K; Keele, Brandon F; Wietgrefe, Stephen W; Fletcher, Courtney V; Beilman, Gregory J; Chipman, Jeffrey G; Khoruts, Alexander; Estes, Jacob D; Anderson, Jodi; Callisto, Samuel P; Schmidt, Thomas E; Thorkelson, Ann; Reilly, Cavan; Perkey, Katherine; Reimann, Thomas G; Utay, Netanya S; Nganou Makamdop, Krystelle; Stevenson, Mario; Douek, Daniel C; Haase, Ashley T; Schacker, Timothy W

    2015-03-10

    Antiretroviral therapy (ART) suppresses HIV replication in most individuals but cannot eradicate latently infected cells established before ART was initiated. Thus, infection rebounds when treatment is interrupted by reactivation of virus production from this reservoir. Currently, one or a few latently infected resting memory CD4 T cells are thought be the principal source of recrudescent infection, but this estimate is based on peripheral blood rather than lymphoid tissues (LTs), the principal sites of virus production and persistence before initiating ART. We, therefore, examined lymph node (LN) and gut-associated lymphoid tissue (GALT) biopsies from fully suppressed subjects, interrupted therapy, monitored plasma viral load (pVL), and repeated biopsies on 12 individuals as soon as pVL became detectable. Isolated HIV RNA-positive (vRNA+) cells were detected by in situ hybridization in LTs obtained before interruption in several patients. After interruption, multiple foci of vRNA+ cells were detected in 6 of 12 individuals as soon as pVL was measureable and in some subjects, in more than one anatomic site. Minimal estimates of the number of rebounding/founder (R/F) variants were determined by single-gene amplification and sequencing of viral RNA or DNA from peripheral blood mononuclear cells and plasma obtained at or just before viral recrudescence. Sequence analysis revealed a large number of R/F viruses representing recrudescent viremia from multiple sources. Together, these findings are consistent with the origins of recrudescent infection by reactivation from many latently infected cells at multiple sites. The inferred large pool of cells and sites to rekindle recrudescent infection highlights the challenges in eradicating HIV.

  5. [Examination of the skull of Stanislaw Papczynski (1631-1701)--the founder of the fraternity of Marian Priests].

    PubMed

    Lorkiewicz-Muszyńska, Dorota; Kociemba, Wojciech; Zaba, Czesław; Lemke, Andrzej

    2009-01-01

    Procedures of identifying an individual on the basis of skeletal remains are of interest to anthropologists, anatomists, morphologists, physicians and criminologists. The results of such procedures are immensely significant, both from the cognitive point of view, as they allow for determining the range of variability of human traits, and from the practical standpoint, in forensic-medical procedures. The methodical aspect of the procedures represents an important problem since the reliability of the employed identification techniques determines the probability with which we can reconstruct the intravital appearance of an individual. The theoretical grounds for the criteria used for person's identification on the basis of skeletal remains are provided by the results of studies on variability of anatomic and morphologic structures and on reciprocal relations between the soft tissues and bony sublayer on which the soft tissues are distributed. Following the process of exhumation on February 12, 2007, in March, we received the skull of Father Stanisław Papczyński, the founder of the fraternity of Marian Priests, with the objective of performing an anthropological examination and reconstructing his face. The examinations were commissioned in association with the ceremony of his beatification planned for September 2007. We used the "POL-SIT Rekonstrukcja" computer-assisted system of intravital face reconstruction, which represents a universal human face reconstruction system, based on the skull pattern introduced to the computer. Computed tomography CT was performed employing a Siemens tomograph Somatom Sensation 64. The 3 D reconstruction of the skull was achieved using the "In Space" software.

  6. Fine localization of the Nijmegen breakage syndrome gene to 8q21: Evidence for a common founder haplotype

    SciTech Connect

    Cerosaletti, K.M.; Lange, E.; Stringham, H.M.

    1998-07-01

    Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, a birdlike face, growth retardation, immunodeficiency, lack of secondary sex characteristics in females, and increased incidence of lymphoid cancers. NBS cells display a phenotype similar to that of cells from ataxia-telangiectasia patients, including chromosomal instability, radiation sensitivity, and aberrant cell-cycle-checkpoint control following exposure to ionizing radiation. A recent study reported genetic linkage of NBs to human chromosome 8q21, with strong linkage disequilibrium detected at marker D8S1811 in eastern European NBS families. The authors collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, the authors report linkage of NBS to 8q21 in 6/7 of these families, with a maximum LOD score of 3.58. Significant linkage disequilibrium was detected for 8/13 markers tested in the 8q21 region, including D8S1811. In order to further localize the gene for NBS, the authors generated a radiation-hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that place the NBS gene between D8S1757 and D8S270. A common founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggest that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88.

  7. Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption

    PubMed Central

    Rothenberger, Meghan K.; Keele, Brandon F.; Wietgrefe, Stephen W.; Fletcher, Courtney V.; Beilman, Gregory J.; Chipman, Jeffrey G.; Khoruts, Alexander; Estes, Jacob D.; Anderson, Jodi; Callisto, Samuel P.; Schmidt, Thomas E.; Thorkelson, Ann; Reilly, Cavan; Perkey, Katherine; Reimann, Thomas G.; Utay, Netanya S.; Nganou Makamdop, Krystelle; Stevenson, Mario; Douek, Daniel C.; Haase, Ashley T.; Schacker, Timothy W.

    2015-01-01

    Antiretroviral therapy (ART) suppresses HIV replication in most individuals but cannot eradicate latently infected cells established before ART was initiated. Thus, infection rebounds when treatment is interrupted by reactivation of virus production from this reservoir. Currently, one or a few latently infected resting memory CD4 T cells are thought be the principal source of recrudescent infection, but this estimate is based on peripheral blood rather than lymphoid tissues (LTs), the principal sites of virus production and persistence before initiating ART. We, therefore, examined lymph node (LN) and gut-associated lymphoid tissue (GALT) biopsies from fully suppressed subjects, interrupted therapy, monitored plasma viral load (pVL), and repeated biopsies on 12 individuals as soon as pVL became detectable. Isolated HIV RNA-positive (vRNA+) cells were detected by in situ hybridization in LTs obtained before interruption in several patients. After interruption, multiple foci of vRNA+ cells were detected in 6 of 12 individuals as soon as pVL was measureable and in some subjects, in more than one anatomic site. Minimal estimates of the number of rebounding/founder (R/F) variants were determined by single-gene amplification and sequencing of viral RNA or DNA from peripheral blood mononuclear cells and plasma obtained at or just before viral recrudescence. Sequence analysis revealed a large number of R/F viruses representing recrudescent viremia from multiple sources. Together, these findings are consistent with the origins of recrudescent infection by reactivation from many latently infected cells at multiple sites. The inferred large pool of cells and sites to rekindle recrudescent infection highlights the challenges in eradicating HIV. PMID:25713386

  8. An ancient autosomal haplotype bearing a rare achromatopsia-causing founder mutation is shared among Arab Muslims and Oriental Jews.

    PubMed

    Zelinger, Lina; Greenberg, Alex; Kohl, Susanne; Banin, Eyal; Sharon, Dror

    2010-09-01

    Numerous cultural aspects, mainly based on historical records, suggest a common origin of the Middle-Eastern Arab Muslim and Jewish populations. This is supported, to some extent, by Y-chromosome haplogroup analysis of Middle-Eastern and European samples. Up to date, no genomic regions that are shared among Arab Muslim and Jewish chromosomes and are unique to these populations have been reported. Here, we report of a rare achromatopsia-causing CNGA3 mutation (c.1585G>A) presents in both Arab Muslim and Oriental Jewish patients. A haplotype analysis of c.1585G>A-bearing chromosomes from Middle Eastern and European origins revealed a shared Muslim-Jewish haplotype, which is different from those detected in European patients, indicating a recurrent mutation stratified by a Jewish-Muslim founder effect. Comprehensive whole-genome haplotype analysis using 250 K single nucleotide polymorphism arrays revealed a large homozygous region of ~11 Mbp shared by both Arab Muslim and Oriental Jewish chromosomes. A subsequent microsatellite analysis of a 21.5 cM interval including CNGA3 and the adjacent chromosome 2 centromere revealed a unique and extremely rare haplotype associated with the c.1585G>A mutation. The age of the shared c.1585G>A mutation was calculated using the microsatellite genotyping data to be about 200 generations ago. A similar analysis of mutation age based on the Arab Muslim data alone showed that the mutation was unlikely to be the product of a recent gene flow event. The data present here demonstrate a large (11 Mbp) genomic region that is likely to originate from an ancient common ancestor of Middle-Eastern Arab Muslims and Jews who lived approximately 5,000 years ago. PMID:20549516

  9. Impact of immune escape mutations on HIV-1 fitness in the context of the cognate transmitted/founder genome

    PubMed Central

    2012-01-01

    Background A modest change in HIV-1 fitness can have a significant impact on viral quasispecies evolution and viral pathogenesis, transmission and disease progression. To determine the impact of immune escape mutations selected by cytotoxic T lymphocytes (CTL) on viral fitness in the context of the cognate transmitted/founder (T/F) genome, we developed a new competitive fitness assay using molecular clones of T/F genomes lacking exogenous genetic markers and a highly sensitive and precise parallel allele-specific sequencing (PASS) method. Results The T/F and mutant viruses were competed in CD4+ T-cell enriched cultures, relative proportions of viruses were assayed after repeated cell-free passage, and fitness costs were estimated by mathematical modeling. Naturally occurring HLA B57-restricted mutations involving the TW10 epitope in Gag and two epitopes in Tat/Rev and Env were assessed independently and together. Compensatory mutations which restored viral replication fitness were also assessed. A principal TW10 escape mutation, T242N, led to a 42% reduction in replication fitness but V247I and G248A mutations in the same epitope restored fitness to wild-type levels. No fitness difference was observed between the T/F and a naturally selected variant carrying the early CTL escape mutation (R355K) in Env and a reversion mutation in the Tat/Rev overlapping region. Conclusions These findings reveal a broad spectrum of fitness costs to CTL escape mutations in T/F viral genomes, similar to recent findings reported for neutralizing antibody escape mutations, and highlight the extraordinary plasticity and adaptive potential of the HIV-1 genome. Analysis of T/F genomes and their evolved progeny is a powerful approach for assessing the impact of composite mutational events on viral fitness. PMID:23110705

  10. Founder haplotype analysis of Fanconi anemia in the Korean population finds common ancestral haplotypes for a FANCG variant.

    PubMed

    Park, Joonhong; Kim, Myungshin; Jang, Woori; Chae, Hyojin; Kim, Yonggoo; Chung, Nack-Gyun; Lee, Jae-Wook; Cho, Bin; Jeong, Dae-Chul; Park, In Yang; Park, Mi Sun

    2015-05-01

    A common ancestral haplotype is strongly suggested in the Korean and Japanese patients with Fanconi anemia (FA), because common mutations have been frequently found: c.2546delC and c.3720_3724delAAACA of FANCA; c.307+1G>C, c.1066C>T, and c.1589_1591delATA of FANCG. Our aim in this study was to investigate the origin of these common mutations of FANCA and FANCG. We genotyped 13 FA patients consisting of five FA-A patients and eight FA-G patients from the Korean FA population. Microsatellite markers used for haplotype analysis included four CA repeat markers which are closely linked with FANCA and eight CA repeat markers which are contiguous with FANCG. As a result, Korean FA-A patients carrying c.2546delC or c.3720_3724delAAACA did not share the same haplotypes. However, three unique haplotypes carrying c.307+1G>C, c.1066C > T, or c.1589_1591delATA, that consisted of eight polymorphic loci covering a flanking region were strongly associated with Korean FA-G, consistent with founder haplotypes reported previously in the Japanese FA-G population. Our finding confirmed the common ancestral haplotypes on the origins of the East Asian FA-G patients, which will improve our understanding of the molecular population genetics of FA-G. To the best of our knowledge, this is the first report on the association between disease-linked mutations and common ancestral haplotypes in the Korean FA population.

  11. Is the Isabella anomaly a fossil slab or the foundered lithospheric root of the Sierra Nevada batholith?

    NASA Astrophysics Data System (ADS)

    Hoots, C. R.; Schmandt, B.; Clayton, R. W.; Hansen, S. M.; Dougherty, S. L.

    2015-12-01

    The Isabella Anomaly is a volume of relatively high seismic velocity upper mantle beneath the southern Great Valley in California. We deployed ~45 broadband seismometers in central California to test two main hypotheses for the origin of the Isabella Anomaly. One suggests that the Isabella Anomaly is the foundered lithospheric root of the southern Sierra Nevada batholith, which delaminated on account of eclogite-rich composition and translated westward as it began to sink into the asthenosphere. The other hypothesis suggests that the Isabella Anomaly is a fossil slab fragment attached to the Monterey microplate that lies offshore of central California and thus it is mechanically coupled to the Pacific plate. Prior seismic imaging with ~70 km station spacing cannot resolve the landward termination of Monterey microplate lithosphere beneath coastal California or where/if the Isabella Anomaly is attached to North America lithosphere beneath the Great Valley. The new temporary broadband array consists of 40 broadband seismometers with ~7 km spacing extending from the central California coast to the western Sierra Nevada batholith, plus some outliers to fill gaps in the regional network coverage. The temporary array was initially deployed in early 2014 and will continue to record until October 2015 so the complete data are not yet available. Preliminary Ps scattered wave images show an abrupt ~6 km increase in Moho depth eastward across the San Andreas fault, a strong positive impedance contrast that dips westward from ~7-25 km beneath Great Valley, and a sharp Moho with a slight westward dip beneath the western edge of the Sierra Nevada batholith. Apparently low impedance contrast characterizes the Moho beneath the eastern Great Valley and foothills, consistent with near mantle velocities in the lower crust. Processing of the cumulative data that will be available in October 2015 and incorporation of new tomography models into scattered wave imaging are needed before

  12. The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction

    PubMed Central

    Odet, Fanny; Pan, Wenqi; Bell, Timothy A.; Goodson, Summer G.; Stevans, Alicia M.; Yun, Zianing; Aylor, David L.; Kao, Chia-Yu; McMillan, Leonard; de Villena, Fernando Pardo-Manuel; O’Brien, Deborah A.

    2015-01-01

    Surveys of inbred strains of mice are standard approaches to determine the heritability and range of phenotypic variation for biomedical traits. In addition, they may lead to the identification of novel phenotypes and models of human disease. Surprisingly, male reproductive phenotypes are among the least-represented traits in the Mouse Phenome Database. Here we report the results of a broad survey of the eight founder inbred strains of both the Collaborative Cross (CC) and the Diversity Outbred populations, two new mouse resources that are being used as platforms for systems genetics and sources of mouse models of human diseases. Our survey includes representatives of the three main subspecies of the house mice and a mix of classical and wild-derived inbred strains. In addition to standard staples of male reproductive phenotyping such as reproductive organ weights, sperm counts, and sperm morphology, our survey includes sperm motility and the first detailed survey of testis histology. As expected for such a broad survey, heritability varies widely among traits. We conclude that although all eight inbred strains are fertile, most display a mix of advantageous and deleterious male reproductive traits. The CAST/EiJ strain is an outlier, with an unusual combination of deleterious male reproductive traits including low sperm counts, high levels of morphologically abnormal sperm, and poor motility. In contrast, sperm from the PWK/PhJ and WSB/EiJ strains had the greatest percentages of normal morphology and vigorous motility. Finally, we report an abnormal testis phenotype that is highly heritable and restricted to the WSB/EiJ strain. This phenotype is characterized by the presence of a large, but variable, number of vacuoles in at least 10% of the seminiferous tubules. The onset of the phenotype between 2 and 3 wk of age is temporally correlated with the formation of the blood-testis barrier. We speculate that this phenotype may play a role in high rates of extinction in

  13. Specific mutations in the HEXA gene among Iraqi Jewish Tay-Sachs disease carriers: dating of founder ancestor.

    PubMed

    Karpati, Mazal; Gazit, Ephraim; Goldman, Boleslaw; Frisch, Amos; Colombo, Roberto; Peleg, Leah

    2004-02-01

    The incidence of Tay-Sachs disease (TSD) carriers, as defined by enzyme assay, is 1:29 among Ashkenazi Jews and 1:110 among Moroccan Jews. An elevated carrier frequency of 1:140 was also observed in the Iraqi Jews (IJ), while in other Israeli populations the world's pan-ethnic frequency of approximately 1:280 has been found. Recently a novel mutation, G749T, has been reported in 38.7% of the IJ carriers (24/62). Here we report a second novel HEXA mutation specific to the IJ TDS carriers: a substitution of cytosine 1351 by guanosine (C1351G), resulting in the change of leucine to valine in position 451. This mutation was found in 33.9% (21/62) of the carriers and in none of 100 non-carrier IJ. In addition to the two specific mutations, 14.5% (9/62) of the IJ carriers bear a known "Jewish" mutation (Ashkenazi or Moroccan) and 11.3% (7/62) carry a known "non-Jewish" mutation. In 1 DNA sample no mutation has yet been detected. To investigate the genetic history of the IJ-specific mutations (C1351G and G749T), the allelic distribution of four polymorphic markers (D15S131, D15S1025, D15S981, D15S1050) was analyzed in IJ heterozygotes and ethnically matched controls. Based on linkage disequilibrium, recombination factor (theta) between the markers and mutated loci, and the population growth correction, we deduced that G749T occurred in a founder ancestor 44.8 +/- 14.2 generations (g) ago [95% confidence interval (CI) 17.0-72.6 g] and C1351G arose 80.4 +/- 35.9 g ago (95% CI 44.5-116.3 g). Thus, the estimated dates for introduction of mutations are: 626 +/- 426 A.D. (200-1052 A.D.) for G749T and 442 +/- 1077 B.C. (1519 B.C. to 635 A.D.) for C1351G. PMID:14648242

  14. Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece

    PubMed Central

    Kitsos, George; Petrou, Zacharias; Grigoriadou, Maria; Samples, John R; Hewitt, Alex W; Kokotas, Haris; Giannoulia-Karantana, Aglaia; Mackey, David A; Wirtz, Mary K; Moschou, Marilita; Ioannidis, John PA; Petersen, Michael B

    2010-01-01

    Background: Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece. Materials and methods: We explored the distribution of the “Greek” T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan–Meier method and the t-test. Results: In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P < 0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD ± 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD ± 11) and 66.8 (SD ± 9.8) years, respectively. Conclusions: The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide. PMID:20390039

  15. The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction.

    PubMed

    Odet, Fanny; Pan, Wenqi; Bell, Timothy A; Goodson, Summer G; Stevans, Alicia M; Yun, Zianing; Aylor, David L; Kao, Chia-Yu; McMillan, Leonard; de Villena, Fernando Pardo-Manuel; O'Brien, Deborah A

    2015-12-01

    Surveys of inbred strains of mice are standard approaches to determine the heritability and range of phenotypic variation for biomedical traits. In addition, they may lead to the identification of novel phenotypes and models of human disease. Surprisingly, male reproductive phenotypes are among the least-represented traits in the Mouse Phenome Database. Here we report the results of a broad survey of the eight founder inbred strains of both the Collaborative Cross (CC) and the Diversity Outbred populations, two new mouse resources that are being used as platforms for systems genetics and sources of mouse models of human diseases. Our survey includes representatives of the three main subspecies of the house mice and a mix of classical and wild-derived inbred strains. In addition to standard staples of male reproductive phenotyping such as reproductive organ weights, sperm counts, and sperm morphology, our survey includes sperm motility and the first detailed survey of testis histology. As expected for such a broad survey, heritability varies widely among traits. We conclude that although all eight inbred strains are fertile, most display a mix of advantageous and deleterious male reproductive traits. The CAST/EiJ strain is an outlier, with an unusual combination of deleterious male reproductive traits including low sperm counts, high levels of morphologically abnormal sperm, and poor motility. In contrast, sperm from the PWK/PhJ and WSB/EiJ strains had the greatest percentages of normal morphology and vigorous motility. Finally, we report an abnormal testis phenotype that is highly heritable and restricted to the WSB/EiJ strain. This phenotype is characterized by the presence of a large, but variable, number of vacuoles in at least 10% of the seminiferous tubules. The onset of the phenotype between 2 and 3 wk of age is temporally correlated with the formation of the blood-testis barrier. We speculate that this phenotype may play a role in high rates of extinction in

  16. Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in South African Afrikaans-speakers.

    PubMed Central

    Starfield, M; Hennies, H C; Jung, M; Jenkins, T; Wienker, T; Hull, P; Spurdle, A; Küster, W; Ramsay, M; Reis, A

    1997-01-01

    Keratolytic winter erythema (KWE), also known as "Oudtshoorn skin disease," or "erythrokeratolysis hiemalis," is an autosomal dominant skin disorder of unknown etiology characterized by a cyclical erythema, hyperkeratosis, and recurrent and intermittent peeling of the palms and soles, particularly during winter. Initially KWE was believed to be unique to South Africa, but recently a large pedigree of German origin has been identified. The disorder occurs with a prevalence of 1/7,000 in the South African Afrikaans-speaking Caucasoid population, and this high frequency has been attributed to founder effect. After a number of candidate regions were excluded from linkage to KWE in both the German family and several South African families, a genomewide analysis was embarked on. Linkage to the microsatellite marker D8S550 on chromosome 8p22-p23 was initially observed, with a maximum LOD score (Z(max)) of 9.2 at a maximum recombination fraction (theta(max)) of .0 in the German family. Linkage was also demonstrated in five of the larger South African families, with Z(max) = 7.4 at theta(max) = .02. When haplotypes were constructed, 11 of 14 South African KWE families had the complete "ancestral" haplotype, and 3 demonstrated conservation of parts of this haplotype, supporting the hypothesis of founder effect. The chromosome segregating with the disease in the German family demonstrated a different haplotype, suggesting that these chromosomes do not have a common origin. Recombination events place the KWE gene in a 6-cM interval between D8S550 and D8S552. If it is assumed that there was a single South African founder, a proposed ancestral recombinant suggests that the gene is most likely in a 1-cM interval between D8S550 and D8S265. PMID:9311742

  17. MSH2 c.1452–1455delAATG Is a Founder Mutation and an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Southern Chinese Population

    PubMed Central

    Chan, Tsun Leung; Wai Chan, Yee; Ho, Judy W. C.; Chan, Celine; Chan, Annie S. Y.; Chan, Emily; Lam, Polly W. Y.; Wah Tse, Chun; Cheong Lee, Kam; Wai Lau, Chi; Gwi, Elaine; Yi Leung, Suet; Yuen, Siu Tsan

    2004-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for ∼2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome. We have previously reported a high incidence of microsatellite instability (MSI) and germline mismatch repair (MMR) gene mutations in young Hong Kong Chinese with CRC. Ongoing studies at the Hereditary Gastrointestinal Cancer Registry in Hong Kong have revealed a unique germline MSH2 c.1452–1455delAATG mutation that has not been reported in other ethnic groups. Detailed analysis showed that this specific MSH2 mutation constituted 21% of all germline MMR gene mutations and 36% of all MSH2 germline mutations identified. We designed a specific PCR-based diagnostic test on paraffin-embedded tissues and identified this germline mutation in 2 (1.5%) of 138 consecutive patients with early-onset CRC (<46 years of age at diagnosis). Haplotype analysis was performed using 11 microsatellite markers located between D2S391 and D2S123. All 10 families had the same disease haplotype, suggesting a founder effect. These 10 families all originated from the Chinese province of Guangdong, which historically included Hong Kong. It is the most populous of the Chinese provinces, with a population of >93 million. Further analysis suggested that this founder mutation may date back to between 22 and 103 generations ago. The identification of this MSH2 founder mutation has important implications for the design of mutation-detection strategies for the southern Chinese population. Since there were major emigrations from Hong Kong and Guangdong province during the 19th and 20th centuries, this finding is also significant for Chinese communities worldwide. PMID:15042510

  18. The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

    SciTech Connect

    Chavez, Leslie L; Perelson, Alan

    2008-01-01

    A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

  19. Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome

    PubMed Central

    2011-01-01

    About 5-10% of breast and ovarian carcinomas are hereditary and most of these result from germline mutations in the BRCA1 and BRCA2 genes. In women of Ashkenazi Jewish ascendance, up to 30% of breast and ovarian carcinomas may be attributable to mutations in these genes, where 3 founder mutations, c.68_69del (185delAG) and c.5266dup (5382insC) in BRCA1 and c.5946del (6174delT) in BRCA2, are commonly encountered. It has been suggested by some authors that screening for founder mutations should be undertaken in all Brazilian women with breast cancer. Thus, the goal of this study was to determine the prevalence of three founder mutations, commonly identified in Ashkenazi individuals in a sample of non-Ashkenazi cancer-affected Brazilian women with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. Among 137 unrelated Brazilian women from HBOC families, the BRCA1c.5266dup mutation was identified in seven individuals (5%). This prevalence is similar to that encountered in non-Ashkenazi HBOC families in other populations. However, among patients with bilateral breast cancer, the frequency of c.5266dup was significantly higher when compared to patients with unilateral breast tumors (12.1% vs 1.2%, p = 0.023). The BRCA1 c.68_69del and BRCA2 c.5946del mutations did not occur in this sample. We conclude that screening non-Ashkenazi breast cancer-affected women from the ethnically heterogeneous Brazilian populations for the BRCA1 c.68_69del and BRCA2 c.5946del is not justified, and that screening for BRCA1c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. In high-risk patients, a negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1 c.5266dup in women with bilateral breast cancer, as well as existence of other as yet unidentified founder mutations in this population, should be further assessed in a larger

  20. Genetic and morphometric evidence on a Galápagos Island exposes founder effects and diversification in the first-known (truly) feral western dog population.

    PubMed

    Reponen, Sini E M; Brown, Sarah K; Barnett, Bruce D; Sacks, Benjamin N

    2014-02-01

    Domesticated animals that revert to a wild state can become invasive and significantly impact native biodiversity. Although dogs can be problematic locally, only the Australasian dingo is known to occur in isolation from humans. Western dogs have experienced more intense artificial selection, which potentially limits their invasiveness. However, feral dogs eradicated from Isabela Island, Galápagos in the 1980s could be the first-known exception. We used DNA and morphometric data from 92 of these dogs to test the hypotheses that (i) these dogs persisted independently of humans for up to a century and a half since descending from a handful of dogs introduced in the early 1800s, vs. (ii) similarly to other western feral dog populations, they reflected continuous recruitment of strays from human settlements on a portion of the Island. We detected one dominant maternal lineage and one dominant paternal lineage shared by the three subpopulations, along with low autosomal genetic diversity, consistent with the hypothesized common origins from a small founder population. Genetic diversity patterns among the three island subpopulations were consistent with stepping-stone founder effects, while morphometric differentiation suggested rapid phenotypic divergence, possibly due to drift and reinforced by selection corresponding to distinct microclimates and habitats on Isabela. Despite the continued presence of free-ranging dogs in the vicinity of settlements on Isabela and other Galápagos Islands, feral populations have not reestablished in remote areas since the 1980s, emphasizing the rarity of conditions necessary for feralization of modern western dogs.

  1. Striking intrafamilial phenotypic variability in Aicardi-Goutières syndrome associated with the recurrent Asian founder mutation in RNASEH2C.

    PubMed

    Vogt, Julie; Agrawal, Shakti; Ibrahim, Zala; Southwood, Taunton R; Philip, Sunny; Macpherson, Lesley; Bhole, Malini V; Crow, Yanick J; Oley, Christine

    2013-02-01

    Aicardi-Goutières syndrome (AGS) is an encephalopathy of early childhood which is most commonly inherited as an autosomal recessive trait. The disorder demonstrates significant genetic heterogeneity with causative mutations in five genes identified to date. Although most patients with AGS experience a severe neonatal or infantile presentation, poor neurodevelopmental outcome and reduced survival, clinical variability in the onset and severity of the condition is being increasingly recognized. A later presentation with a more variable effect on development, morbidity and mortality has been particularly observed in association with mutations in SAMHD1 and RNASEH2B. In contrast, the recurrent c.205C > T (p.R69W) RNASEH2C Asian founder mutation has previously only been identified in children with a severe AGS phenotype. Here, to our knowledge, we present the first report of marked phenotypic variability in siblings both harboring this founder mutation in the homozygous state. In this family, one female child had a severe AGS phenotype with an onset in infancy and profound developmental delay, whilst an older sister was of completely normal intellect with a normal head circumference and was only diagnosed because of the presence of chilblains and a mild hemiplegia. An appreciation of intrafamilial phenotypic expression is important in the counseling of families considering prenatal diagnosis, and may also be relevant to the assessment of efficacy in future clinical trials. In addition, marked phenotypic variation raises the possibility that more mildly affected patients are not currently identified. PMID:23322642

  2. A 1,100-year-old founder effect mutation in IL12B gene is responsible for Mendelian susceptibility to mycobacterial disease in Tunisian patients.

    PubMed

    Ben-Mustapha, Imen; Ben-Ali, Meriem; Mekki, Najla; Patin, Etienne; Harmant, Christine; Bouguila, Jihène; Elloumi-Zghal, Houda; Harbi, Abdelaziz; Béjaoui, Mohamed; Boughammoura, Lamia; Chemli, Jalel; Barbouche, Mohamed-Ridha

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare disorder predisposing apparently healthy individuals to infections caused by weakly virulent mycobacteria such as bacille Calmette-Guerin (BCG), environmental mycobacteria, and poorly virulent Salmonella strains. IL-12p40 deficiency is the first reported human disease due to a cytokine gene defect and is one of the deficiencies that cause MSMD. Nine mutant alleles only have been identified in the IL12B gene, and three of them are recurrent mutations due to a founder effect in specific populations. IL-12p40 deficiency has been identified especially in countries where consanguinity is high and where BCG vaccination at birth is universal. We investigated, in such settings, the clinical, cellular, and molecular features of six IL-12p40-deficient Tunisian patients having the same mutation in IL12B gene (c.298_305del). We found that this mutation is inherited as a common founder mutation arousing ~1,100 years ago. This finding facilitates the development of a preventive approach by genetic counseling and prenatal diagnosis especially in affected families.

  3. Analysis of Founder Mutations in Rare Tumors Associated With Hereditary Breast/Ovarian Cancer Reveals a Novel Association of BRCA2 Mutations with Ampulla of Vater Carcinomas.

    PubMed

    Pinto, Pedro; Peixoto, Ana; Santos, Catarina; Rocha, Patrícia; Pinto, Carla; Pinheiro, Manuela; Leça, Luís; Martins, Ana Teresa; Ferreira, Verónica; Bartosch, Carla; Teixeira, Manuel R

    2016-01-01

    BRCA1 and BRCA2 mutations are responsible for hereditary breast and ovarian cancer, but they also confer an increased risk for the development of rarer cancers associated with this syndrome, namely, cancer of the pancreas, male breast, peritoneum, and fallopian tube. The objective of this work was to quantify the contribution of the founder mutations BRCA2 c.156_157insAlu and BRCA1 c.3331_3334del for cancer etiology in unselected hospital-based cohorts of Portuguese patients diagnosed with these rarer cancers, by using a strategy that included testing of archival tumor tissue. A total of 102 male breast, 68 pancreatic and 33 peritoneal/fallopian tube carcinoma cases were included in the study. The BRCA2 c.156_157insAlu mutation was observed with a frequency of 7.8% in male breast cancers, 3.0% in peritoneal/fallopian tube cancers, and 1.6% in pancreatic cancers, with estimated total contributions of germline BRCA2 mutations of 14.3%, 5.5%, and 2.8%, respectively. No carriers of the BRCA1 c.3331_3334del mutation were identified. During our study, a patient with an ampulla of Vater carcinoma was incidentally found to carry the BRCA2 c.156_157insAlu mutation, so we decided to test a consecutive series of additional 15 ampullary carcinomas for BRCA1/BRCA2 mutations using a combination of direct founder mutation testing and full gene analysis with next generation sequencing. BRCA2 mutations were observed with a frequency of 14.3% in ampulla of Vater carcinomas. In conclusion, taking into account the implications for both the individuals and their family members, we recommend that patients with these neoplasias should be offered BRCA1/BRCA2 genetic testing and we here show that it is feasible to test for founder mutations in archival tumor tissue. Furthermore, we identified for the first time a high frequency of germline BRCA2 mutations in ampullary cancers. PMID:27532258

  4. Analysis of Founder Mutations in Rare Tumors Associated With Hereditary Breast/Ovarian Cancer Reveals a Novel Association of BRCA2 Mutations with Ampulla of Vater Carcinomas

    PubMed Central

    Pinto, Pedro; Peixoto, Ana; Santos, Catarina; Rocha, Patrícia; Pinto, Carla; Pinheiro, Manuela; Leça, Luís; Martins, Ana Teresa; Ferreira, Verónica; Bartosch, Carla

    2016-01-01

    BRCA1 and BRCA2 mutations are responsible for hereditary breast and ovarian cancer, but they also confer an increased risk for the development of rarer cancers associated with this syndrome, namely, cancer of the pancreas, male breast, peritoneum, and fallopian tube. The objective of this work was to quantify the contribution of the founder mutations BRCA2 c.156_157insAlu and BRCA1 c.3331_3334del for cancer etiology in unselected hospital-based cohorts of Portuguese patients diagnosed with these rarer cancers, by using a strategy that included testing of archival tumor tissue. A total of 102 male breast, 68 pancreatic and 33 peritoneal/fallopian tube carcinoma cases were included in the study. The BRCA2 c.156_157insAlu mutation was observed with a frequency of 7.8% in male breast cancers, 3.0% in peritoneal/fallopian tube cancers, and 1.6% in pancreatic cancers, with estimated total contributions of germline BRCA2 mutations of 14.3%, 5.5%, and 2.8%, respectively. No carriers of the BRCA1 c.3331_3334del mutation were identified. During our study, a patient with an ampulla of Vater carcinoma was incidentally found to carry the BRCA2 c.156_157insAlu mutation, so we decided to test a consecutive series of additional 15 ampullary carcinomas for BRCA1/BRCA2 mutations using a combination of direct founder mutation testing and full gene analysis with next generation sequencing. BRCA2 mutations were observed with a frequency of 14.3% in ampulla of Vater carcinomas. In conclusion, taking into account the implications for both the individuals and their family members, we recommend that patients with these neoplasias should be offered BRCA1/BRCA2 genetic testing and we here show that it is feasible to test for founder mutations in archival tumor tissue. Furthermore, we identified for the first time a high frequency of germline BRCA2 mutations in ampullary cancers. PMID:27532258

  5. Sexually-Transmitted/Founder HIV-1 Cannot Be Directly Predicted from Plasma or PBMC-Derived Viral Quasispecies in the Transmitting Partner

    PubMed Central

    Frange, Pierre; Meyer, Laurence; Jung, Matthieu; Goujard, Cecile; Zucman, David; Abel, Sylvie; Hochedez, Patrick; Gousset, Marine; Gascuel, Olivier; Rouzioux, Christine; Chaix, Marie-Laure

    2013-01-01

    Objective Characterization of HIV-1 sequences in newly infected individuals is important for elucidating the mechanisms of viral sexual transmission. We report the identification of transmitted/founder viruses in eight pairs of HIV-1 sexually-infected patients enrolled at the time of primary infection (“recipients”) and their transmitting partners (“donors”). Methods Using a single genome-amplification approach, we compared quasispecies in donors and recipients on the basis of 316 and 376 C2V5 env sequences amplified from plasma viral RNA and PBMC-associated DNA, respectively. Results Both DNA and RNA sequences indicated very homogeneous viral populations in all recipients, suggesting transmission of a single variant, even in cases of recent sexually transmitted infections (STIs) in donors (n = 2) or recipients (n = 3). In all pairs, the transmitted/founder virus was derived from an infrequent variant population within the blood of the donor. The donor variant sequences most closely related to the recipient sequences were found in plasma samples in 3/8 cases and/or in PBMC samples in 6/8 cases. Although donors were exclusively (n = 4) or predominantly (n = 4) infected by CCR5-tropic (R5) strains, two recipients were infected with highly homogeneous CXCR4/dual-mixed-tropic (X4/DM) viral populations, identified in both DNA and RNA. The proportion of X4/DM quasispecies in donors was higher in cases of X4/DM than R5 HIV transmission (16.7–22.0% versus 0–2.6%), suggesting that X4/DM transmission may be associated with a threshold population of X4/DM circulating quasispecies in donors. Conclusions These suggest that a severe genetic bottleneck occurs during subtype B HIV-1 heterosexual and homosexual transmission. Sexually-transmitted/founder virus cannot be directly predicted by analysis of the donor’s quasispecies in plasma and/or PBMC. Additional studies are required to fully understand the traits that confer the capacity to transmit and

  6. High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus.

    PubMed

    Bogdanova, N V; Antonenkova, N N; Rogov, Y I; Karstens, J H; Hillemanns, P; Dörk, T

    2010-10-01

    Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital-based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first-degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first-degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non-carriers. Taken together, these results

  7. Mapping the gene for hereditary hyperparathyroidism and prolactinoma (MENI[sub Burin]) to chromosome 11q: Evidence for a founder effect in patients from Newfoundland

    SciTech Connect

    Petty, E.M.; Bale, A.E. ); Green, J.S. ); Marx, S.J. ); Taggart, R.T. ); Farid, N. )

    1994-06-01

    An autosomal dominant syndrome of prolactinomas, carcinoids, and hyperparathyroidism was described in four Newfoundland kindreds in 1980 and in one kindred from the Pacific Northwest in 1983. Because this syndrome shares many features with multiple endocrine neoplasia type 1, the gene for which maps to proximal chromosome 11q, the authors performed linkage studies with chromosome 11 markers in prolactinoma families to determine whether the two genes map to the same location. All proximal chromosome 11q markers gave positive LOD scores, and no recombinants were seen with PYGM (LOD score 15.25, recombination fraction .0). All affected individuals from Newfoundland shared the same PYGM allele, providing evidence for a founder effect. The disease in the Pacific Northwest kindred cosegregated with a different PYGM allele. 32 refs., 2 figs., 3 tabs.

  8. Genetic variability, differentiation, and founder effect in golden jackals (Canis aureus) from Serbia as revealed by mitochondrial DNA and nuclear microsatellite loci.

    PubMed

    Zachos, Frank E; Cirovic, Dusko; Kirschning, Julia; Otto, Marthe; Hartl, Günther B; Petersen, Britt; Honnen, Ann-Christin

    2009-04-01

    We analyzed 121 golden jackals (Canis aureus) from six sample sites in Serbia with regard to genetic variability and differentiation as revealed by mitochondrial control region sequences and eight nuclear microsatellite loci. There was no variation at all in the mtDNA sequences, and nuclear variability was very low (average observed and expected heterozygosity of 0.29 and 0.34, respectively). This is in line with the considerable recent range expansion of this species in the Balkans and indicates a strong founder effect in the recently established Serbian population. We did not find evidence of differentiation between the northeastern jackals and those from the plain of Srem or those in between. F-statistics and Bayesian Structure analyses, however, were indicative of a low degree of overall differentiation in the Serbian population. A vagrant Austrian jackal that was also analyzed was genetically indistinguishable from its Serbian conspecifics. PMID:19169806

  9. Genetic variability, differentiation, and founder effect in golden jackals (Canis aureus) from Serbia as revealed by mitochondrial DNA and nuclear microsatellite loci.

    PubMed

    Zachos, Frank E; Cirovic, Dusko; Kirschning, Julia; Otto, Marthe; Hartl, Günther B; Petersen, Britt; Honnen, Ann-Christin

    2009-04-01

    We analyzed 121 golden jackals (Canis aureus) from six sample sites in Serbia with regard to genetic variability and differentiation as revealed by mitochondrial control region sequences and eight nuclear microsatellite loci. There was no variation at all in the mtDNA sequences, and nuclear variability was very low (average observed and expected heterozygosity of 0.29 and 0.34, respectively). This is in line with the considerable recent range expansion of this species in the Balkans and indicates a strong founder effect in the recently established Serbian population. We did not find evidence of differentiation between the northeastern jackals and those from the plain of Srem or those in between. F-statistics and Bayesian Structure analyses, however, were indicative of a low degree of overall differentiation in the Serbian population. A vagrant Austrian jackal that was also analyzed was genetically indistinguishable from its Serbian conspecifics.

  10. Genetic and biochemical study of dual hereditary jaundice: Dubin-Johnson and Gilbert's syndromes. Haplotyping and founder effect of deletion in ABCC2.

    PubMed

    Slachtova, Lenka; Seda, Ondrej; Behunova, Jana; Mistrik, Martin; Martasek, Pavel

    2016-05-01

    Dual hereditary jaundice, a combination of Dubin-Johnson and Gilbert's syndromes, is a rare clinical entity resulting from the compound defects of bilirubin conjugation and transport. We aimed to study the hereditary jaundice in 56 members from seven seemingly unrelated Roma families, to find the causal genetic defect and to estimate its origin in Roma population. On the basis of biochemical results of total and conjugated serum bilirubin and clinical observations, ABCC2 gene, TATA box and phenobarbital enhancer (PBREM) of UGT1A1 gene were analyzed by sequencing, RFLP and fragment analysis. We found a novel variant c.1013_1014delTG in the eighth exon of ABCC2 gene in 17 individuals in homozygous state. Dual defect NG_011798.1:c.[1013_1014delTG]; NG_002601.2:g.[175492_175493insTA] in homozygous state was found in four subjects. Biochemical analyses of porphyrins and coproporphyrin isomers in urine performed by HPLC showed inverted ratio of excreted coproporphyrin, with the predominance of coproporphyrin I (up to 100%), typical for patients with Dubin-Johnson syndrome. Pursuant cultural and social specifics of the population led us to suspect a founder effect; therefore, we performed a haplotype study using genotyping data from Affymetrix Genome-Wide Human SNP Array 6.0. As a result, we detected a common 86 kbp haplotype encompassing promoter and part of the ABCC2 coding region among all families, and estimated the age of the ancestral variant to 178-185 years. In this study, we found a novel deletion in ABCC2 gene, described genetic and biochemical features of dual hereditary jaundice and confirmed the existence of founder effect and common haplotype among seven Roma families.

  11. Formation of low-δ18O magmas of the Kangerlussuaq Intrusion by addition of water derived from dehydration of foundered basaltic roof rocks

    NASA Astrophysics Data System (ADS)

    Riishuus, Morten S.; Harris, Chris; Peate, David W.; Tegner, Christian; Wilson, J. Richard; Brooks, C. Kent

    2015-05-01

    The Kangerlussuaq Intrusion in East Greenland is concentrically zoned from quartz nordmarkite (quartz syenite) at the margin, through pulaskite, to foyaite (nepheline syenite) in the centre, with no apparent intrusive contacts. The δ18O values of coexisting minerals are consistent with oxygen isotope equilibrium at magmatic temperatures. Most of the intrusion formed from low-δ18O magma; magma δ18O values generally increased upwards from about 3.3 ‰ in the quartz nordmarkites to 5.6 ‰ in the foyaites. The lowest magma δ18O value of about -1.0 ‰ is from the upper part of the nordmarkites, where there is a high concentration of foundered basaltic xenoliths (stoped from the roof of the intrusion). The amphiboles in the syenites have δD values that range from those typical of hydrous mantle-derived minerals to much lower values (-86 to -157 ‰), as do whole-rock samples of xenolith and country rock (-125 to -148 ‰). The low magma δ18O and δD values are consistent with continuous incorporation, exchange and upward escape of low-δ18O and δD fluids released from stoped basaltic roof material. Mass balance suggests that the integrated amount of water involved was 7 wt% of the volume of the magma, but locally reached 30 wt% water. The requirement for large amounts of water with low δ18O value is satisfied only if the foundered basalt contained most of its water in cavities as opposed to hydrous minerals. Even with this requirement, the volume of stoped basalt would have been equal to the volume of the magma. Repeated recharge of the residual magma with progressively less contaminated silica undersaturated melt resulted in a gradual shift across the low-pressure thermal divide. Crystallisation was suppressed by the depression of the liquidus due to water saturation of the residual magma (pH2O ~1 kbar).

  12. Rapid Buildup of Genetic Diversity in Founder Populations of the Gynodioecious Plant Species Origanum vulgare after Semi-Natural Grassland Restoration

    PubMed Central

    Helsen, Kenny; Jacquemyn, Hans; Hermy, Martin; Vandepitte, Katrien; Honnay, Olivier

    2013-01-01

    In most landscapes the success of habitat restoration is largely dependent on spontaneous colonization of plant species. This colonization process, and the outcome of restoration practices, can only be considered successful if the genetic makeup of founding populations is not eroded through founder effects and subsequent genetic drift. Here we used 10 microsatellite markers to investigate the genetic effects of recent colonization of the long-lived gynodioecious species Origanum vulgare in restored semi-natural grassland patches. We compared the genetic diversity and differentiation of fourteen recent populations with that of thirteen old, putative source populations, and we evaluated the effects of spatial configuration of the populations on colonization patterns. We did not observe decreased genetic diversity in recent populations, or inflated genetic differentiation among them. Nevertheless, a significantly higher inbreeding coefficient was observed in recent populations, although this was not associated with negative fitness effects. Overall population genetic differentiation was low (FST = 0.040). Individuals of restored populations were assigned to on average 6.1 different source populations (likely following the ‘migrant pool’ model). Gene flow was, however, affected by the spatial configuration of the grasslands, with gene flow into the recent populations mainly originating from nearby source populations. This study demonstrates how spontaneous colonization after habitat restoration can lead to viable populations in a relatively short time, overcoming pronounced founder effects, when several source populations are nearby. Restored populations can therefore rapidly act as stepping stones and sources of genetic diversity, likely increasing overall metapopulation viability of the study species. PMID:23840642

  13. Hidden founder effects: small-scale spatial genetic structure in recently established populations of the grassland specialist plant Anthyllis vulneraria.

    PubMed

    Helsen, Kenny; Jacquemyn, Hans; Honnay, Olivier

    2015-06-01

    The long-term establishment success of founder plant populations has been commonly assessed based on the measures of population genetic diversity and among population genetic differentiation, with founder populations expected to carry sufficient genetic diversity when population establishment is the result of many colonists from multiple source populations (the 'migrant pool' colonization model). Theory, however, predicts that, after initial colonization, rapid population expansion may result in a fast increase in the extent of spatial genetic structure (SGS), independent of extant genetic diversity. This SGS can reduce long-term population viability by increasing inbreeding. Using 12 microsatellite markers, we inferred colonization patterns in four recent populations of the grassland specialist plant Anthyllis vulneraria and compared the extent of SGS between recently established and old populations. Assignment analyses of the individuals of recent population based on the genetic composition of nine adjacent putative source populations suggested the occurrence of the 'migrant pool' colonization model, further confirmed by high genetic diversity within and low genetic differentiation among recent populations. Population establishment, however, resulted in the build-up of strong SGS, most likely as a result of spatially restricted recruitment of the progeny of initial colonists. Although reduced, significant SGS was nonetheless observed to persist in old populations. The presence of SGS was in all populations associated with elevated inbreeding coefficients, potentially affecting the long-term viability of these populations. In conclusion, this study illustrates the importance of studying SGS next to population genetic diversity and differentiation to adequately infer colonization patterns and long-term establishment success of plant species.

  14. Genetic and morphometric evidence on a Galápagos Island exposes founder effects and diversification in the first-known (truly) feral western dog population.

    PubMed

    Reponen, Sini E M; Brown, Sarah K; Barnett, Bruce D; Sacks, Benjamin N

    2014-02-01

    Domesticated animals that revert to a wild state can become invasive and significantly impact native biodiversity. Although dogs can be problematic locally, only the Australasian dingo is known to occur in isolation from humans. Western dogs have experienced more intense artificial selection, which potentially limits their invasiveness. However, feral dogs eradicated from Isabela Island, Galápagos in the 1980s could be the first-known exception. We used DNA and morphometric data from 92 of these dogs to test the hypotheses that (i) these dogs persisted independently of humans for up to a century and a half since descending from a handful of dogs introduced in the early 1800s, vs. (ii) similarly to other western feral dog populations, they reflected continuous recruitment of strays from human settlements on a portion of the Island. We detected one dominant maternal lineage and one dominant paternal lineage shared by the three subpopulations, along with low autosomal genetic diversity, consistent with the hypothesized common origins from a small founder population. Genetic diversity patterns among the three island subpopulations were consistent with stepping-stone founder effects, while morphometric differentiation suggested rapid phenotypic divergence, possibly due to drift and reinforced by selection corresponding to distinct microclimates and habitats on Isabela. Despite the continued presence of free-ranging dogs in the vicinity of settlements on Isabela and other Galápagos Islands, feral populations have not reestablished in remote areas since the 1980s, emphasizing the rarity of conditions necessary for feralization of modern western dogs. PMID:24261528

  15. Posterior microphthalmia and nanophthalmia in Tunisia caused by a founder c.1059_1066insC mutation of the PRSS56 gene.

    PubMed

    Said, Mariem Ben; Chouchène, Ebtissem; Salem, Salma Ben; Daoud, Kods; Largueche, Leila; Bouassida, Walid; Benzina, Zeineb; Ayadi, Hammadi; Söderkvist, Peter; Matri, Leila; Hmani-Aifa, Mounira

    2013-10-10

    Congenital microphthalmia (CMIC) is a common developmental ocular disorder characterized by a small, and sometimes malformed, eye. Posterior microphthalmia (PM) and nanophthalmia are two rare subtypes of isolated CMIC characterized by extreme hyperopia due to short axial length and elevated lens/eye volume ratio. While nanophthalmia is associated with a reduced size in both anterior and posterior segments, PM involves a normal-size anterior chamber but a small posterior segment. Several genes encoding transcription and non-transcription regulators have been identified in different forms of CMIC. MFRP gene mutations have, for instance, been associated with nanophthalmia, and mutations in the recently identified PRSS56 gene have been linked to PM. So far, these two forms of CMIC have been associated with 9 mutations in PRSS56. Of particular interest, a c.1059_1066insC mutation has recently been reported in four Tunisian families with isolated PM and one Tunisian family with nanophthalmia. Here, we performed a genome-wide scan using a high density single nucleotide polymorphism (SNP) array 50 K in a large consanguineous Tunisian family (PM7) affected with PM and identified the same causative disease mutation. A total of 24 polymorphic markers spanning the PRSS56 gene in 6 families originating from different regions of Tunisia were analyzed to investigate the origin of the c.1059_1066insC mutation and to determine whether it arose in a common ancestor. A highly significant disease-associated haplotype, spanning across the 146 kb of the 2q37.1 chromosome, was conserved in those families, suggesting that c.1059_1066insC arose from a common founder. The age of the mutation in this haplotype was estimated to be around 1,850 years. The identification of such 'founder effects' may greatly simplify diagnostic genetic screening and lead to better prognostic counseling.

  16. Comparison of multiple genotyping methods for the identification of the cancer predisposing founder mutation p.R337H in TP53.

    PubMed

    Fitarelli-Kiehl, Mariana; Macedo, Gabriel S; Schlatter, Rosane Paixão; Koehler-Santos, Patricia; Matte, Ursula da Silveira; Ashton-Prolla, Patricia; Giacomazzi, Juliana

    2016-06-01

    Germline mutations in the TP53 gene are associated with Li-Fraumeni and Li-Fraumeni-Like Syndromes, characterized by increased predisposition to early-onset cancers. In Brazil, the prevalence of the TP53-p.R337H germline mutation is exceedingly high in the general population and in cancer-affected patients, probably as result of a founder effect. Several genotyping methods are used for the molecular diagnosis of LFS/LFL, however Sanger sequencing is still considered the gold standard. We compared performance, cost and turnaround time of Sanger sequencing, PCR-RFLP, TaqMan-PCR and HRM in the p.R337H genotyping. The performance was determined by analysis of 95 genomic DNA samples and results were 100% concordant for all methods. Sequencing was the most expensive method followed by TaqMan-PCR, PCR-RFLP and HRM. The overall cost of HRM increased with the prevalence of positive samples, since confirmatory sequencing must be performed when a sample shows an abnormal melting profile, but remained lower than all other methods when the mutation prevalence was less than 2.5%. Sequencing had the highest throughput and the longest turnaround time, while TaqMan-PCR showed the lowest turnaround and hands-on times. All methodologies studied are suitable for the detection of p.R337H and the choice will depend on the application and clinical scenario. PMID:27275664

  17. A novel Gypsy founder mutation, p.Arg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes

    PubMed Central

    Gooding, R; Colomer, J; King, R; Angelicheva, D; Marns, L; Parman, Y; Chandler, D; Bertranpetit, J; Kalaydjieva, L

    2005-01-01

    Background: Linkage, haplotype and sequencing analysis in a large Spanish Gypsy kindred with multiple members affected by autosomal recessive peripheral neuropathy led to the identification of a novel mutation, p.Arg1109X, in the CMT4C gene. The screening of further unrelated patients, and of a panel of ethnically matched controls, showed that p.Arg1109X is an ancestral mutation which occurs in Gypsy populations across Europe and is the most common cause of autosomal recessive Charcot–Marie–Tooth disease in Spanish Gypsies. Objective: To report the identification of a novel Gypsy founder mutation causing autosomal recessive CMT4C disease in a sample of homozygous affected individuals. Results: The mutation was associated with a surprisingly broad spectrum of neuropathy phenotypes, with variation in the age at onset, rate of progression, severity of muscle and sensory involvement, the presence of scoliosis, and cranial nerve involvement. Conclusions: Ascertainment and further studies of CMT4C patients in this population will provide a unique opportunity for characterising the full range of clinical manifestations of the disease in a genetically homogeneous sample. PMID:16326826

  18. Advancing paternal age at birth is associated with poorer social functioning earlier and later in life of schizophrenia patients in a founder population.

    PubMed

    Liebenberg, Rudolf; van Heerden, Brigitte; Ehlers, René; Du Plessis, Anna M E; Roos, J Louw

    2016-09-30

    Consistent associations have been found between advanced paternal age and an increased risk of psychiatric disorders, such as schizophrenia, in their offspring. This increase appears to be linear as paternal age increases. The present study investigates the relationship between early deviant behaviour in the first 10 years of life of patients as well as longer term functional outcome and paternal age in sporadic Afrikaner founder population cases of schizophrenia. This might improve our understanding of Paternal Age-Related Schizophrenia (PARS). Follow-up psychiatric diagnoses were confirmed by the Diagnostic Interview for Genetic Studies (DIGS). An early deviant childhood behaviour semi-structured questionnaire and the Specific Level of Functioning Assessment (SLOF) were completed. From the logistic regression models fitted, a significant negative relationship was found between paternal age at birth and social dysfunction as early deviant behaviour. Additionally, regression analysis revealed a significant negative relationship between paternal age at birth and the SLOF for interpersonal relationships later in life. Early social dysfunction may represent a phenotypic trait for PARS. Further research is required to understand the relationship between early social dysfunction and deficits in interpersonal relationships later in life. PMID:27416538

  19. Cerebrotendinous xanthomatosis: Possibility of founder mutation in CYP27A1 gene (c.526delG) in Eastern Indian and Surinamese population.

    PubMed

    Dutta, Atanu Kumar; Danda, Sumita; Muthusamy, Karthik; Alexander, Mathew; Sudhakar, Sniya Valsa; Hansdak, Samuel; Bandyopadhyay, Rini; Bakhya Shree, G B; Rekha, L

    2015-06-01

    Cerebrotendinous xanthomatosis is a lipid storage disease characterized by diarrhea, cataract, tendon xanthoma and neurological regression if untreated. CYP27A1 is the only gene in which mutations are known to cause Cerebrotendinous xanthomatosis. We report two Indian families from different regions of India who underwent molecular testing of CYP27A1. The first family from Eastern India consisting of two affected individuals was found to have the c.526delG homozygous mutation in exon 3, previously reported from our laboratory, also in a patient from Eastern India. However the second affected individual from Southern India that we studied and two previously reported cases from Northern India have different mutations. Interestingly the only previous report of c.526delG mutation was in a Surinamese individual from the Netherlands. To date most of the pathogenic mutations for Cerebrotendinous xanthomatosis have been confined to single population except for R362C mutation which was reported from the Netherlands and the USA (Black). To our knowledge this is the second causal mutation for Cerebrotendinous xanthomatosis which has been reported in two different populations. As human trading was prevalent from Eastern India to Surinam by the Dutch settlers this mutation might suggest a common founder mutation in these populations.

  20. Detection of BRCA1 and BRCA2 Ashkenazi Jewish founder mutations in formalin-fixed paraffin-embedded tissues using conventional PCR and heteroduplex/amplicon size differences.

    PubMed

    Mangold, Kathy A; Wang, Vivien; Weissman, Scott M; Rubinstein, Wendy S; Kaul, Karen L

    2010-01-01

    In many families with histories suggestive of BRCA1- or BRCA2-related disease, the proband is deceased. Reliable assessment of archived tissue blocks not amenable to full gene sequencing would be helpful. In this study, a polymerase chain reaction (PCR) assay using primers that bracket the BRCA mutation site and microfluidics-based detection of heteroduplex/amplicon size differences was developed to circumvent artifacts associated with low quality DNA from formalin-fixed paraffin-embedded (FFPE) tissue. Genomic DNA was extracted from 100 FFPE specimens from patients that had previously undergone BRCA gene sequence analysis on blood specimens. Conventional PCR amplification products were differentiated using the Agilent 2100 Bioanalyzer. One FFPE specimen failed to amplify the wild-type alleles for all three sites and was therefore called indeterminate. All 62 FFPE specimens with known Ashkenazi Jewish founder mutations had both the wild-type and the correct mutated allele amplified, including one specimen that failed to amplify the mutant allele in other real-time PCR assays. Appropriately, 21 FFPE specimens known to have other BRCA1/2 mutations and 16 without any mutation had only the wild-type allele correctly amplified for each target. Therefore, by changing the primer location and detecting amplicons via heteroduplexes formed by size differences, we identified mutations from FFPE tissues missed using real-time methods.

  1. Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome.

    PubMed

    Cartault, François; Munier, Patrick; Jacquemont, Marie-Line; Vellayoudom, Jeannine; Doray, Bérénice; Payet, Christine; Randrianaivo, Hanitra; Laville, Jean-Marc; Munnich, Arnold; Cormier-Daire, Valérie

    2015-01-01

    First described as a variant of Larsen syndrome in Reunion Island (LRS) in the southern Indian Ocean, 'Larsen of Reunion Island syndrome' is characterized by dwarfism, hyperlaxity, multiple dislocations and distinctive facial features. It overlaps with Desbuquois dysplasia, Larsen syndrome and spondyloepiphyseal dysplasia with dislocations ascribed to CANT1, FLNB and CHST3 mutations, respectively. We collected the samples of 22 LRS cases. After exclusion of CANT1, FLNB and CHST3 genes, an exome sequencing was performed in two affected second cousins and one unaffected sister. We identified a homozygous missense mutation in B4GALT7, NM_007255.2: c.808C>T p.(Arg270Cys) named p.R270C, in the two affected cases, not present in the unaffected sister. The same homozygous mutation was subsequently identified in the remaining 20 LRS cases. Our findings demonstrate that B4GALT7 is the causative gene for LRS. The identification of a unique homozygous mutation argues in favor of a founder effect. B4GALT7 encodes a galactosyltransferase, required for the initiation of glycoaminoglycan side chain synthesis of proteoglycans. This study expands the phenotypic spectrum of B4GALT7 mutations, initially described as responsible for the progeroid variant of Ehlers-Danlos syndrome. It further supports a common physiopathological basis involving proteoglycan synthesis in skeletal disorders with dislocations. PMID:24755949

  2. Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.

    PubMed

    Sharma, Swarkar; Saha, Anjana; Rai, Ekta; Bhat, Audesh; Bamezai, Ramesh

    2005-01-01

    We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.

  3. Sensitivity of transmitted and founder human immunodeficiency virus type 1 envelopes to carbohydrate-binding agents griffithsin, cyanovirin-N and Galanthus nivalis agglutinin.

    PubMed

    Hu, Bodan; Du, Tao; Li, Chang; Luo, Sukun; Liu, Yalan; Huang, Xin; Hu, Qinxue

    2015-12-01

    Human immunodeficiency virus type 1 (HIV-1) transmission often results from infection by a single transmitted/founder (T/F) virus. Here, we investigated the sensitivity of T/F HIV-1 envelope glycoproteins (Envs) to microbicide candidate carbohydrate-binding agents (CBAs) griffithsin (GRFT), cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA), showing that T/F Envs demonstrated different sensitivity to CBAs, with IC50 values ranging from 0.006 ± 0.0003 to >10 nM for GRFT, from 0.6 ± 0.2 to 28.9 ± 2.9 nM for CV-N and from 1.3 ± 0.2 to >500 nM for GNA. We further revealed that deglycosylation at position 295 or 448 decreased the sensitivity of T/F Env to GRFT, and at 339 to both CV-N and GNA. Mutation of all the three glcyans rendered a CBA-sensitive T/F Env largely resistant to GRFT, indicating that the sensitivity of T/F Env to GRFT is mainly determined by glycans at 295, 339 and 448. Our study identified specific T/F Env residues associated with CBA sensitivity.

  4. Comparison of multiple genotyping methods for the identification of the cancer predisposing founder mutation p.R337H inTP53

    PubMed Central

    Fitarelli-Kiehl, Mariana; Macedo, Gabriel S.; Schlatter, Rosane Paixão; Koehler-Santos, Patricia; Matte, Ursula da Silveira; Ashton-Prolla, Patricia; Giacomazzi, Juliana

    2016-01-01

    Abstract Germline mutations in the TP53 gene are associated with Li-Fraumeni and Li-Fraumeni-Like Syndromes, characterized by increased predisposition to early-onset cancers. In Brazil, the prevalence of the TP53-p.R337H germline mutation is exceedingly high in the general population and in cancer-affected patients, probably as result of a founder effect. Several genotyping methods are used for the molecular diagnosis of LFS/LFL, however Sanger sequencing is still considered the gold standard. We compared performance, cost and turnaround time of Sanger sequencing, PCR-RFLP, TaqMan-PCR and HRM in the p.R337H genotyping. The performance was determined by analysis of 95 genomic DNA samples and results were 100% concordant for all methods. Sequencing was the most expensive method followed by TaqMan-PCR, PCR-RFLP and HRM. The overall cost of HRM increased with the prevalence of positive samples, since confirmatory sequencing must be performed when a sample shows an abnormal melting profile, but remained lower than all other methods when the mutation prevalence was less than 2.5%. Sequencing had the highest throughput and the longest turnaround time, while TaqMan-PCR showed the lowest turnaround and hands-on times. All methodologies studied are suitable for the detection of p.R337H and the choice will depend on the application and clinical scenario. PMID:27275664

  5. A novel MERTK deletion is a common founder mutation in the Faroe Islands and is responsible for a high proportion of retinitis pigmentosa cases

    PubMed Central

    Duno, Morten; Batbayli, Mustafa; Vilhelmsen, Kaj; Rosenberg, Thomas

    2011-01-01

    Purpose The aim of the study was to elucidate the genetic background of retinitis pigmentosa (RP) in a Faroe Islands population, a genetic isolate in the North Atlantic Ocean. Methods Blood samples were collected from subjects diagnosed with RP and their families. DNA from affected individuals underwent single nucleotide polymorphism microarray analysis and homozygosity mapping followed by sequence analysis of candidate genes. Results We identified 25 cases of nonsyndromic RP corresponding to a prevalence of 1 in 1,900. Single nucleotide polymorphism analysis revealed a homozygous region on chromosome 2q, common to patients in four families, which harbored the RP gene MER tyrosine kinase protooncogene (MERTK). A deletion of 91 kb was identified in seven patients, representing 30% of the analyzed Faroese cases of nonsyndromic RP. The clinical course of six patients who were homozygous for the deletion showed onset in the first decade followed by a rapid deterioration of both rod and cone photoreceptor function. Early macular involvement was present, in accordance with that of other reported patients with MERTK mutations. Conclusions Previous studies have shown a frequency of less than 1% of MERTK mutations in RP patients. The 91-kb deletion encompassing exons 1–7 of MERTK is a common founder mutation in the Faroe Islands, responsible for around 30% of RP, and together with mutations in protocadherin 21 (PCDH21) accounts for more than half of the retinal dystrophy cases. PMID:21677792

  6. A highly recombined, high-density, eight-founder wheat MAGIC map reveals extensive segregation distortion and genomic locations of introgression segments.

    PubMed

    Gardner, Keith A; Wittern, Lukas M; Mackay, Ian J

    2016-06-01

    Multiparent Advanced Generation Intercross (MAGIC) mapping populations offer unique opportunities and challenges for marker and QTL mapping in crop species. We have constructed the first eight-parent MAGIC genetic map for wheat, comprising 18 601 SNP markers. We validated the accuracy of our map against the wheat genome sequence and found an improvement in accuracy compared to published genetic maps. Our map shows a notable increase in precision resulting from the three generations of intercrossing required to create the population. This is most pronounced in the pericentromeric regions of the chromosomes. Sixteen percent of mapped markers exhibited segregation distortion (SD) with many occurring in long (>20 cM) blocks. Some of the longest and most distorted blocks were collinear with noncentromeric high-marker-density regions of the genome, suggesting they were candidates for introgression fragments introduced into the bread wheat gene pool from other grass species. We investigated two of these linkage blocks in detail and found strong evidence that one on chromosome 4AL, showing SD against the founder Robigus, is an interspecific introgression fragment. The completed map is available from http://www.niab.com/pages/id/326/Resources.

  7. The initiation of lateral roots in the primary roots of maize (Zea mays L.) implies a reactivation of cell proliferation in a group of founder pericycle cells.

    PubMed

    Alarcón, M Victoria; Lloret, Pedro G; Martín-Partido, Gervasio; Salguero, Julio

    2016-03-15

    The initiation of lateral roots (LRs) has generally been viewed as a reactivation of proliferative activity in pericycle cells that are committed to initiate primordia. However, it is also possible that pericycle founder cells that initiate LRs never cease proliferative activity but rather are displaced to the most distal root zones while undertaking successive stages of LR initiation. In this study, we tested these two alternative hypotheses by examining the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the DNA of meristematic root cells of Zea mays. According to the values for the length of the cell cycle and values for cell displacement along the maize root, our results strongly suggest that pericycle cells that initiate LR primordia ceased proliferative activity upon exiting the meristematic zone. This finding is supported by the existence of a root zone between 4 and 20mm from the root cap junction, in which neither mitotic cells nor labelled nuclei were observed in phloem pericycle cells. PMID:26905196

  8. Very low-depth sequencing in a founder population identifies a cardioprotective APOC3 signal missed by genome-wide imputation

    PubMed Central

    Gilly, Arthur; Ritchie, Graham Rs; Southam, Lorraine; Farmaki, Aliki-Eleni; Tsafantakis, Emmanouil; Dedoussis, George; Zeggini, Eleftheria

    2016-01-01

    Cohort-wide very low-depth whole-genome sequencing (WGS) can comprehensively capture low-frequency sequence variation for the cost of a dense genome-wide genotyping array. Here, we analyse 1x sequence data across the APOC3 gene in a founder population from the island of Crete in Greece (n = 1239) and find significant evidence for association with blood triglyceride levels with the previously reported R19X cardioprotective null mutation (β = −1.09,σ = 0.163, P = 8.2 × 10−11) and a second loss of function mutation, rs138326449 (β = −1.17,σ = 0.188, P = 1.14 × 10−9). The signal cannot be recapitulated by imputing genome-wide genotype data on a large reference panel of 5122 individuals including 249 with 4x WGS data from the same population. Gene-level meta-analysis with other studies reporting burden signals at APOC3 provides robust evidence for a replicable cardioprotective rare variant aggregation (P = 3.2 × 10−31, n = 13 480). PMID:27146844

  9. Eduardo Primo Yúfera, founder of Revista de Agroquímica y Tecnología de Alimentos and pioneer on food science and technology research in Spain.

    PubMed

    Ayala-Gascón, M; Aleixandre-Benavent, R; Gandía-Balaguer, A

    2011-12-01

    Eduardo Primo Yúfera was the founder and director of the Instituto de Agroquímica y Tecnología de Alimentos (IATA, 1957-1974) until he was appointed president of the Consejo Superior de Investigaciones Científicas (CSIC). His aim to publicize food science led him to create the Revista de Agroquímica y Tecnología de Alimentos in 1961, the forerunner of this journal, Food Science and Technology International, which he directed until 1977. Of his scientific output, 50% has been published in this journal. He is considered to be the promoter and exponent of Food Science and Technology and Chemical Ecology in Spain as well as the instigator of the country's innovation model (R&D and innovation). In his work, he was able to combine basic research excellence and socially relevant applied research to move both science and society forward. He was an example and inspiration to many colleagues and followers. The aim of this study is to highlight the influence and importance of Primo Yúfera in the formation, development and consolidation of the journal Revista de Agroquímica y Tecnología de Alimentos, and to appraise his scientific contribution to this journal.

  10. Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome

    PubMed Central

    Cartault, François; Munier, Patrick; Jacquemont, Marie-Line; Vellayoudom, Jeannine; Doray, Bérénice; Payet, Christine; Randrianaivo, Hanitra; Laville, Jean-Marc; Munnich, Arnold; Cormier-Daire, Valérie

    2015-01-01

    First described as a variant of Larsen syndrome in Reunion Island (LRS) in the southern Indian Ocean, ‘Larsen of Reunion Island syndrome' is characterized by dwarfism, hyperlaxity, multiple dislocations and distinctive facial features. It overlaps with Desbuquois dysplasia, Larsen syndrome and spondyloepiphyseal dysplasia with dislocations ascribed to CANT1, FLNB and CHST3 mutations, respectively. We collected the samples of 22 LRS cases. After exclusion of CANT1, FLNB and CHST3 genes, an exome sequencing was performed in two affected second cousins and one unaffected sister. We identified a homozygous missense mutation in B4GALT7, NM_007255.2: c.808C>T p.(Arg270Cys) named p.R270C, in the two affected cases, not present in the unaffected sister. The same homozygous mutation was subsequently identified in the remaining 20 LRS cases. Our findings demonstrate that B4GALT7 is the causative gene for LRS. The identification of a unique homozygous mutation argues in favor of a founder effect. B4GALT7 encodes a galactosyltransferase, required for the initiation of glycoaminoglycan side chain synthesis of proteoglycans. This study expands the phenotypic spectrum of B4GALT7 mutations, initially described as responsible for the progeroid variant of Ehlers–Danlos syndrome. It further supports a common physiopathological basis involving proteoglycan synthesis in skeletal disorders with dislocations. PMID:24755949

  11. High carriers frequency of an apparently ancient founder mutation p.Tyr322X in the ERCC8 gene responsible for Cockayne syndrome among Christian Arabs in Northern Israel.

    PubMed

    Khayat, Morad; Hardouf, Hagar; Zlotogora, Joel; Shalev, Stavit Allon

    2010-12-01

    Most autosomal recessive diseases are rare in the general population, but in genetically isolated communities specific condition might be frequent, mainly due to founder effect. Recognition of common inherited disorders in defined populations may be effective in improving public health care. Cockayne syndrome (CS) is a rare autosomal recessive disorder common in Christian Arabs due to a p.Tyr322X mutation. Genetic screening of the p.Tyr322X mutation of the ERCC8 gene in this population documented a carrier frequency of 6.79% (95% confidence interval: 3.84-9.74%). The haplotype analysis data, as well as the high carriers frequency of CS, suggested that the Israeli Arab Christian CS mutation (p.Tyr322X) is an ancient founder mutation that may have originated in the Christian Lebanese community. As a result of this pilot study the Christian CS mutation was included in the genetic screening program offered to the Israeli Arab Christian community.

  12. Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length

    PubMed Central

    Kell, Alison; Stoddard, Mark; Li, Hui; Marcotrigiano, Joe; Shaw, George M.

    2015-01-01

    ABSTRACT Despite the introduction of direct-acting antiviral (DAA) drugs against hepatitis C virus (HCV), infection remains a major public health concern because DAA therapeutics do not prevent reinfection and patients can still progress to chronic liver disease. Chronic HCV infection is supported by a variety of viral immune evasion strategies, but, remarkably, 20% to 30% of acute infections spontaneously clear prior to development of adaptive immune responses, thus implicating innate immunity in resolving acute HCV infection. However, the virus-host interactions regulating acute infection are unknown. Transmission of HCV involves one or a few transmitted/founder (T/F) variants. In infected hepatocytes, the retinoic acid-inducible gene I (RIG-I) protein recognizes 5′ triphosphate (5′ppp) of the HCV RNA and a pathogen-associated molecular pattern (PAMP) motif located within the 3′ untranslated region consisting of poly-U/UC. PAMP binding activates RIG-I to induce innate immune signaling and type 1 interferon antiviral defenses. HCV poly-U/UC sequences can differ in length and complexity, suggesting that PAMP diversity in T/F genomes could regulate innate immune control of acute HCV infection. Using 14 unique poly-U/UC sequences from HCV T/F genomes recovered from acute-infection patients, we tested whether RIG-I recognition and innate immune activation correlate with PAMP sequence characteristics. We show that T/F variants are recognized by RIG-I in a manner dependent on length of the U-core motif of the poly-U/UC PAMP and are recognized by RIG-I to induce innate immune responses that restrict acute infection. PAMP recognition of T/F HCV variants by RIG-I may therefore impart innate immune signaling and HCV restriction to impact acute-phase-to-chronic-phase transition. IMPORTANCE Recognition of nonself molecular patterns such as those seen with viral nucleic acids is an essential step in triggering the immune response to virus infection. Innate immunity is

  13. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression.

    PubMed

    Eiberg, Hans; Troelsen, Jesper; Nielsen, Mette; Mikkelsen, Annemette; Mengel-From, Jonas; Kjaer, Klaus W; Hansen, Lars

    2008-03-01

    The human eye color is a quantitative trait displaying multifactorial inheritance. Several studies have shown that the OCA2 locus is the major contributor to the human eye color variation. By linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region within the HERC2 gene. By association analyses, we identified two SNPs within this region that were perfectly associated with the blue and brown eye colors: rs12913832 and rs1129038. Of these, rs12913832 is located 21.152 bp upstream from the OCA2 promoter in a highly conserved sequence in intron 86 of HERC2. The brown eye color allele of rs12913832 is highly conserved throughout a number of species. As shown by a Luciferase assays in cell cultures, the element significantly reduces the activity of the OCA2 promoter and electrophoretic mobility shift assays demonstrate that the two alleles bind different subsets of nuclear extracts. One single haplotype, represented by six polymorphic SNPs covering half of the 3' end of the HERC2 gene, was found in 155 blue-eyed individuals from Denmark, and in 5 and 2 blue-eyed individuals from Turkey and Jordan, respectively. Hence, our data suggest a common founder mutation in an OCA2 inhibiting regulatory element as the cause of blue eye color in humans. In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color.

  14. The roles of geography and founder effects in promoting host-associated differentiation in the generalist bogus yucca moth Prodoxus decipiens.

    PubMed

    Darwell, C T; Fox, K A; Althoff, D M

    2014-12-01

    There is ample evidence that host shifts in plant-feeding insects have been instrumental in generating the enormous diversity of insects. Changes in host use can cause host-associated differentiation (HAD) among populations that may lead to reproductive isolation and eventual speciation. The importance of geography in facilitating this process remains controversial. We examined the geographic context of HAD in the wide-ranging generalist yucca moth Prodoxus decipiens. Previous work demonstrated HAD among sympatric moth populations feeding on two different Yucca species occurring on the barrier islands of North Carolina, USA. We assessed the genetic structure of P. decipiens across its entire geographic and host range to determine whether HAD is widespread in this generalist herbivore. Population genetic analyses of microsatellite and mtDNA sequence data across the entire range showed genetic structuring with respect to host use and geography. In particular, genetic differentiation was relatively strong between mainland populations and those on the barrier islands of North Carolina. Finer scale analyses, however, among sympatric populations using different host plant species only showed significant clustering based on host use for populations on the barrier islands. Mainland populations did not form population clusters based on host plant use. Reduced genetic diversity in the barrier island populations, especially on the derived host, suggests that founder effects may have been instrumental in facilitating HAD. In general, results suggest that the interplay of local adaptation, geography and demography can determine the tempo of HAD. We argue that future studies should include comprehensive surveys across a wide range of environmental and geographic conditions to elucidate the contribution of various processes to HAD.

  15. Autosomal Dominant Retinal Dystrophies Caused by a Founder Splice Site Mutation, c.828+3A>T, in PRPH2 and Protein Haplotypes in trans as Modifiers

    PubMed Central

    Shankar, Suma P.; Hughbanks-Wheaton, Dianna K.; Birch, David G.; Sullivan, Lori S.; Conneely, Karen N.; Bowne, Sara J.; Stone, Edwin M.; Daiger, Stephen P.

    2016-01-01

    Purpose We determined the phenotypic variation, disease progression, and potential modifiers of autosomal dominant retinal dystrophies caused by a splice site founder mutation, c.828+3A>T, in the PRPH2 gene. Methods A total of 62 individuals (19 families) harboring the PRPH2 c.828+3A>T mutation, had phenotype analysis by fundus appearance, electrophysiology, and visual fields. The PRPH2 haplotypes in trans were sequenced for potential modifying variants and generalized estimating equations (GEE) used for statistical analysis. Results Several distinct phenotypes caused by the PRPH2 c.828+3A>T mutation were observed and fell into two clinical categories: Group I (N = 44) with mild pattern dystrophies (PD) and Group II (N = 18) with more severe cone-rod dystrophy (CRD), retinitis pigmentosa (RP), and central areolar chorioretinal dystrophy (CACD). The PRPH2 Gln304-Lys310-Asp338 protein haplotype in trans was found in Group I only (29.6% vs. 0%), whereas the Glu304-Lys310-Gly338 haplotype was predominant in Group II (94.4% vs. 70.4%). Generalized estimating equations analysis for PD versus the CRD/CACD/RP phenotypes in individuals over 43 years alone with the PRPH2 haplotypes in trans and age as predictors, adjusted for correlation within families, confirmed a significant effect of haplotype on severity (P = 0.03) with an estimated odds ratio of 7.16 (95% confidence interval [CI] = [2.8, 18.4]). Conclusions The PRPH2 c.828+3A>T mutation results in multiple distinct phenotypes likely modified by protein haplotypes in trans; the odds of having the CACD/RP-like phenotype (versus the PD phenotype) are 7.16 times greater with a Glu304-Lys310-Gly338 haplotype in trans. Further functional studies of the modifying haplotypes in trans and PRPH2 splice variants may offer therapeutic targets. PMID:26842753

  16. Dock mediates Scar- and WASp-dependent actin polymerization through interaction with cell adhesion molecules in founder cells and fusion-competent myoblasts

    PubMed Central

    Kaipa, Balasankara Reddy; Shao, Huanjie; Schäfer, Gritt; Trinkewitz, Tatjana; Groth, Verena; Liu, Jianqi; Beck, Lothar; Bogdan, Sven; Abmayr, Susan M.; Önel, Susanne-Filiz

    2013-01-01

    Summary The formation of the larval body wall musculature of Drosophila depends on the asymmetric fusion of two myoblast types, founder cells (FCs) and fusion-competent myoblasts (FCMs). Recent studies have established an essential function of Arp2/3-based actin polymerization during myoblast fusion, formation of a dense actin focus at the site of fusion in FCMs, and a thin sheath of actin in FCs and/or growing muscles. The formation of these actin structures depends on recognition and adhesion of myoblasts that is mediated by cell surface receptors of the immunoglobulin superfamily. However, the connection of the cell surface receptors with Arp2/3-based actin polymerization is poorly understood. To date only the SH2-SH3 adaptor protein Crk has been suggested to link cell adhesion with Arp2/3-based actin polymerization in FCMs. Here, we propose that the SH2-SH3 adaptor protein Dock, like Crk, links cell adhesion with actin polymerization. We show that Dock is expressed in FCs and FCMs and colocalizes with the cell adhesion proteins Sns and Duf at cell–cell contact points. Biochemical data in this study indicate that different domains of Dock are involved in binding the cell adhesion molecules Duf, Rst, Sns and Hbs. We emphasize the importance of these interactions by quantifying the enhanced myoblast fusion defects in duf dock, sns dock and hbs dock double mutants. Additionally, we show that Dock interacts biochemically and genetically with Drosophila Scar, Vrp1 and WASp. Based on these data, we propose that Dock links cell adhesion in FCs and FCMs with either Scar– or Vrp1–WASp-dependent Arp2/3 activation. PMID:22992459

  17. Double PALB2 and BRCA1/BRCA2 mutation carriers are rare in breast cancer and breast-ovarian cancer syndrome families from the French Canadian founder population

    PubMed Central

    ANCOT, FRÉDÉRIC; ARCAND, SUZANNA L.; MES-MASSON, ANNE-MARIE; PROVENCHER, DIANE M.; TONIN, PATRICIA N.

    2015-01-01

    French Canadian families with breast cancer and breast-ovarian cancer syndrome harbor specific BRCA1, BRCA2 and PALB2 germline mutations, which have been attributed to common founders. Mutations in these genes confer an increased risk to breast and ovarian cancers, and have been identified to play a role in and directly interact with the common homologous recombination DNA repair pathways. Our previous study described the case of a female diagnosed with breast cancer at 45 years old, who harbored the PALB2:c.2323C>T [p.Q775X] and BRCA2:c.9004G>A [p.E3002K] germline mutations, which have been found to recur in the French Canadian cancer families. As the frequency of double heterozygous carriers of breast-ovarian cancer susceptibility alleles is unknown, and due to the possibility that there may be implications for genetic counseling and management for these carriers, the present study investigated the co-occurrence of BRCA1/BRCA2 and PALB2 mutations in the French Canadian cancer families. The PALB2:c.2323C>T [p.Q775X] mutation, which is the only PALB2 mutation to have been identified in French Canadian cancer families, was screened in 214 breast cancer cases and 22 breast-ovarian cancer cases from 114 BRCA1/BRCA2 mutation-positive French Canadian breast cancer (n=61) and breast-ovarian cancer (n=53) families using a tailored polymerase chain reaction-based TaqMan® SNP Genotyping Assay. No additional PALB2:c.2323C>T [p.Q775X] mutation carriers were identified among the BRCA1/BRCA2 mutation carriers. The results suggest that carriers of the PALB2:c.2323C>T [p.Q775X] mutation rarely co-occur in French Canadian breast cancer and breast-ovarian cancer families harboring BRCA1 or BRCA2 mutations. PMID:26137147

  18. Dock mediates Scar- and WASp-dependent actin polymerization through interaction with cell adhesion molecules in founder cells and fusion-competent myoblasts.

    PubMed

    Kaipa, Balasankara Reddy; Shao, Huanjie; Schäfer, Gritt; Trinkewitz, Tatjana; Groth, Verena; Liu, Jianqi; Beck, Lothar; Bogdan, Sven; Abmayr, Susan M; Önel, Susanne-Filiz

    2013-01-01

    The formation of the larval body wall musculature of Drosophila depends on the asymmetric fusion of two myoblast types, founder cells (FCs) and fusion-competent myoblasts (FCMs). Recent studies have established an essential function of Arp2/3-based actin polymerization during myoblast fusion, formation of a dense actin focus at the site of fusion in FCMs, and a thin sheath of actin in FCs and/or growing muscles. The formation of these actin structures depends on recognition and adhesion of myoblasts that is mediated by cell surface receptors of the immunoglobulin superfamily. However, the connection of the cell surface receptors with Arp2/3-based actin polymerization is poorly understood. To date only the SH2-SH3 adaptor protein Crk has been suggested to link cell adhesion with Arp2/3-based actin polymerization in FCMs. Here, we propose that the SH2-SH3 adaptor protein Dock, like Crk, links cell adhesion with actin polymerization. We show that Dock is expressed in FCs and FCMs and colocalizes with the cell adhesion proteins Sns and Duf at cell-cell contact points. Biochemical data in this study indicate that different domains of Dock are involved in binding the cell adhesion molecules Duf, Rst, Sns and Hbs. We emphasize the importance of these interactions by quantifying the enhanced myoblast fusion defects in duf dock, sns dock and hbs dock double mutants. Additionally, we show that Dock interacts biochemically and genetically with Drosophila Scar, Vrp1 and WASp. Based on these data, we propose that Dock links cell adhesion in FCs and FCMs with either Scar- or Vrp1-WASp-dependent Arp2/3 activation.

  19. Evolutionary History of the Live-Bearing Endemic Allotoca diazi Species Complex (Actinopterygii, Goodeinae): Evidence of Founder Effect Events in the Mexican Pre-Hispanic Period.

    PubMed

    Corona-Santiago, Diushi Keri; Doadrio, Ignacio; Domínguez-Domínguez, Omar

    2015-01-01

    The evolutionary history of Mexican ichthyofauna has been strongly linked to natural events, and the impact of pre-Hispanic cultures is little known. The live-bearing fish species Allotoca diazi, Allotoca meeki and Allotoca catarinae occur in areas of biological, cultural and economic importance in central Mexico: Pátzcuaro basin, Zirahuén basin, and the Cupatitzio River, respectively. The species are closely related genetically and morphologically, and hypotheses have attempted to explain their systematics and biogeography. Mitochondrial DNA and microsatellite markers were used to investigate the evolutionary history of the complex. The species complex shows minimal genetic differentiation. The separation of A. diazi and A. meeki was dated to 400-7000 years ago, explained by geological and climate events. A bottleneck and reduction of genetic diversity in Allotoca diazi was detected, attributed to recent climate fluctuations and anthropogenic activity. The isolation of A. catarinae occurred ~1900 years ago. No geological events are documented in the area during this period, but the date is contemporary with P'urhépecha culture settlements. This founder effect represents the first evidence of fish species translocation by a pre-Hispanic culture of Mexico. The response of the complex to climate fluctuation, geological changes and human activity in the past and the future according to the ecological niches predictions indicates areas of vulnerability and important information for conservation. The new genetic information showed that the Allotoca diazi complex consist of two genetic groups with an incomplete lineage sorting pattern: Pátzcuaro and Zirahuén lakes, and an introduced population in the Cupatitzio River.

  20. The roles of geography and founder effects in promoting host-associated differentiation in the generalist bogus yucca moth Prodoxus decipiens.

    PubMed

    Darwell, C T; Fox, K A; Althoff, D M

    2014-12-01

    There is ample evidence that host shifts in plant-feeding insects have been instrumental in generating the enormous diversity of insects. Changes in host use can cause host-associated differentiation (HAD) among populations that may lead to reproductive isolation and eventual speciation. The importance of geography in facilitating this process remains controversial. We examined the geographic context of HAD in the wide-ranging generalist yucca moth Prodoxus decipiens. Previous work demonstrated HAD among sympatric moth populations feeding on two different Yucca species occurring on the barrier islands of North Carolina, USA. We assessed the genetic structure of P. decipiens across its entire geographic and host range to determine whether HAD is widespread in this generalist herbivore. Population genetic analyses of microsatellite and mtDNA sequence data across the entire range showed genetic structuring with respect to host use and geography. In particular, genetic differentiation was relatively strong between mainland populations and those on the barrier islands of North Carolina. Finer scale analyses, however, among sympatric populations using different host plant species only showed significant clustering based on host use for populations on the barrier islands. Mainland populations did not form population clusters based on host plant use. Reduced genetic diversity in the barrier island populations, especially on the derived host, suggests that founder effects may have been instrumental in facilitating HAD. In general, results suggest that the interplay of local adaptation, geography and demography can determine the tempo of HAD. We argue that future studies should include comprehensive surveys across a wide range of environmental and geographic conditions to elucidate the contribution of various processes to HAD. PMID:25403722

  1. Evolutionary History of the Live-Bearing Endemic Allotoca diazi Species Complex (Actinopterygii, Goodeinae): Evidence of Founder Effect Events in the Mexican Pre-Hispanic Period

    PubMed Central

    Corona-Santiago, Diushi Keri; Doadrio, Ignacio; Domínguez-Domínguez, Omar

    2015-01-01

    The evolutionary history of Mexican ichthyofauna has been strongly linked to natural events, and the impact of pre-Hispanic cultures is little known. The live-bearing fish species Allotoca diazi, Allotoca meeki and Allotoca catarinae occur in areas of biological, cultural and economic importance in central Mexico: Pátzcuaro basin, Zirahuén basin, and the Cupatitzio River, respectively. The species are closely related genetically and morphologically, and hypotheses have attempted to explain their systematics and biogeography. Mitochondrial DNA and microsatellite markers were used to investigate the evolutionary history of the complex. The species complex shows minimal genetic differentiation. The separation of A. diazi and A. meeki was dated to 400–7000 years ago, explained by geological and climate events. A bottleneck and reduction of genetic diversity in Allotoca diazi was detected, attributed to recent climate fluctuations and anthropogenic activity. The isolation of A. catarinae occurred ~1900 years ago. No geological events are documented in the area during this period, but the date is contemporary with P’urhépecha culture settlements. This founder effect represents the first evidence of fish species translocation by a pre-Hispanic culture of Mexico. The response of the complex to climate fluctuation, geological changes and human activity in the past and the future according to the ecological niches predictions indicates areas of vulnerability and important information for conservation. The new genetic information showed that the Allotoca diazi complex consist of two genetic groups with an incomplete lineage sorting pattern: Pátzcuaro and Zirahuén lakes, and an introduced population in the Cupatitzio River. PMID:25946217

  2. Genetic structure of the poplar rust fungus Melampsora larici-populina: evidence for isolation by distance in Europe and recent founder effects overseas.

    PubMed

    Barrès, Benoît; Halkett, Fabien; Dutech, Cyril; Andrieux, Axelle; Pinon, Jean; Frey, Pascal

    2008-09-01

    Dispersal has a great impact on the genetic structure of populations, but remains difficult to estimate by direct measures. In particular, gradual and stochastic dispersal are often difficult to assess and to distinguish, although they have different evolutionary consequences. Plant pathogens, especially rust fungi, are suspected to display both dispersal modes, though on different spatial scales. In this study, we inferred dispersal capacities of the poplar rust fungus Melampsora larici-populina by examining the genetic diversity and structure of 13 populations from eight European and two overseas countries in the Northern hemisphere. M. larici-populina was sampled from both cultivated hybrid poplars and on the wild host, Populus nigra. The populations were analyzed with 11 microsatellite and 8 virulence markers. Although isolates displayed different virulence profiles according to the host plant, neutral markers revealed little population differentiation with respect to the type of host. This suggests an absence of reproductive isolation between populations sampled from cultivated and wild poplars. Conversely, studying the relationship between geographic and genetic structure allowed us to distinguish between isolation by distance (IBD) patterns and long distance dispersal (LDD) events. The European populations exhibited a significant IBD pattern, suggesting a regular and gradual dispersal of the pathogen over this spatial scale. Nonetheless, the genetic differentiation between these populations was low, suggesting an important gene flow on a continental scale. The two overseas populations from Iceland and Canada were shown to result from rare LDD events, and exhibited signatures of strong founder effects. Furthermore, the high genetic differentiation between both populations suggested that these two recent introductions were independent. This study illustrated how the proper use of population genetics methods can enable contrasted dispersal modes to be revealed.

  3. Genetic diversity in the gypsy moth fungal pathogen Entomophaga maimaiga from founder populations in North America and source populations in Asia.

    PubMed

    Nielsen, Charlotte; Milgroom, Michael G; Hajek, Ann E

    2005-08-01

    Entomophaga maimaiga is a naturally occurring fungal pathogen specific to larvae of the gypsy moth, Lymantria dispar. E. maimaiga is thought to be native to Asia where its epizootics can suppress gypsy moth outbreaks. However, in the USA this beneficial fungal pathogen was not observed until 1989, although an isolate of E. maimaiga from Tokyo was released in Massachusetts to control gypsy moths as early as in 1910-1911, and another isolate from Ishikawa Prefecture in Japan was later released in 1985 and 1986 in New York and Virginia. Our objectives were to: (1) test the hypothesis that E. maimaiga populations in the USA have reduced genetic variability due to founder effects compared to the putative ancestral populations in Asia; (2) track the origin of the North American populations of this fungus; and (3) assess whether genetic differences among E. maimaiga isolates are correlated to morphological differences. We compared genetic diversity among 30 E. maimaiga isolates originating from seven states in the USA, five prefectures in Japan, one province of China and one region of far eastern Russia by AFLPs. Among 14 USA isolates, only ten polymorphic AFLP loci were found, whereas 56 polymorphic loci were found among 16 Asian isolates; 29 loci were polymorphic among 12 isolates from Japan alone. Average gene diversity (h) for the polymorphic loci was 0.223 +/- 0.005 for Asia (including Japan), 0.131 +/- 0.006 for Japan only, and 0.041 +/- 0.004 for the USA. Thus, native populations from Asia were more diverse than the USA populations. These results are consistent with the expectation of a population founded from a source population by a small number of individuals. Distance and parsimony analyses of AFLP data showed that the isolates from the USA formed one distinct clade that was most closely related to Japanese isolates collected outside the Tokyo area. No morphological variation of E. maimaiga from different geographical locations was detected.

  4. An epidemiological investigation of a Forkhead box protein E3 founder mutation underlying the high frequency of sclerocornea, aphakia, and microphthalmia in a Mexican village

    PubMed Central

    Pantoja-Melendez, Carlos; Ali, Manir

    2013-01-01

    Purpose To investigate the molecular epidemiological basis for the unusually high incidence of sclerocornea, aphakia, and microphthalmia in a village in the Tlaxcala province of central Mexico. Methods A population census was performed in a village to identify all sclerocornea, aphakia, and microphthalmia cases. Molecular analysis of the previously identified Forkhead box protein E3 (FOXE3) mutation, c.292T>C (p.Y98H), was performed with PCR amplification and direct DNA sequencing. In addition, DNA from 405 randomly selected unaffected villagers was analyzed to establish the carrier frequency of the causal mutation. To identify the number of generations since the mutation arose in the village, 17 polymorphic markers distributed in a region of 6 Mb around the mutated locus were genotyped in the affected individuals, followed by DMLE software analysis to calculate mutation age. Results A total of 22 patients with sclerocornea, aphakia, and microphthalmia were identified in the village, rendering a disease prevalence of 2.52 cases per 1,000 habitants (1 in 397). The FOXE3 homozygous mutation was identified in all 17 affected subjects who consented to molecular analysis. Haplotype analysis indicated that the mutation arose 5.0–6.5 generations ago (approximately 106–138 years). Among the 405 unaffected villagers who were genotyped, ten heterozygote carriers were identified, yielding a population carrier frequency of approximately 1 in 40 and a predicted incidence of affected of 1 in 6,400 based on random marriages between two carriers in the village. Conclusions This study demonstrates that a cluster of patients with sclerocornea, aphakia, and microphthalmia in a small Mexican village is due to a FOXE3 p.Y98H founder mutation that arose in the village just over a century ago at a time when a population migrated from a nearby village because of land disputes. The actual disease incidence is higher than the calculated predicted value and suggests non-random marriages

  5. Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

    PubMed Central

    Liao, Hua-Xin; Pollara, Justin; Liu, Pinghuang; Alam, S. Munir; Zhang, Ruijun; Cocklin, Sarah L.; Shen, Xiaoying; Duffy, Ryan; Xia, Shi-Mao; Schutte, Robert J.; Pemble IV, Charles W.; Dennison, S. Moses; Li, Hui; Chao, Andrew; Vidnovic, Kora; Evans, Abbey; Klein, Katja; Kumar, Amit; Robinson, James; Landucci, Gary; Forthal, Donald N.; Montefiori, David C.; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.; Soderberg, Kelly A.; Giorgi, Elena E.; Blair, Lily; Korber, Bette T.; Moog, Christiane; Shattock, Robin J.; Schmitz, Joern E.; Moody, M. A.; Gao, Feng; Ferrari, Guido; Shaw, George M.; Haynes, Barton F.

    2015-01-01

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses. PMID:26237403

  6. Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques

    SciTech Connect

    Santra, Sampa; Tomaras, Georgia D.; Warrier, Ranjit; Nicely, Nathan I.; Liao, Hua -Xin; Pollara, Justin; Liu, Pinghuang; Alam, S. Munir; Zhang, Ruijun; Cocklin, Sarah L.; Shen, Xiaoying; Duffy, Ryan; Xia, Shi -Mao; Schutte, Robert J.; Pemble IV, Charles W.; Dennison, S. Moses; Li, Hui; Chao, Andrew; Vidnovic, Kora; Evans, Abbey; Klein, Katja; Kumar, Amit; Robinson, James; Landucci, Gary; Forthal, Donald N.; Montefiori, David C.; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.; Soderberg, Kelly A.; Giorgi, Elena E.; Blair, Lily; Korber, Bette T.; Moog, Christiane; Shattock, Robin J.; Letvin, Norman L.; Schmitz, Joern E.; Moody, M. A.; Gao, Feng; Ferrari, Guido; Shaw, George M.; Haynes, Barton F.; Douek, Daniel C.

    2015-08-03

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4⁺ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

  7. Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques

    DOE PAGES

    Santra, Sampa; Tomaras, Georgia D.; Warrier, Ranjit; Nicely, Nathan I.; Liao, Hua -Xin; Pollara, Justin; Liu, Pinghuang; Alam, S. Munir; Zhang, Ruijun; Cocklin, Sarah L.; et al

    2015-08-03

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4⁺ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant regionmore » of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.« less

  8. Occurrence of genetic drift and founder effect during quasispecies evolution of the VP2 and NS3/NS3A genes of bluetongue virus upon passage between sheep, cattle, and Culicoides sonorensis.

    PubMed

    Bonneau, K R; Mullens, B A; MacLachlan, N J

    2001-09-01

    Bluetongue virus (BTV) is the cause of an insect-transmitted virus infection of ruminants that occurs throughout much of the world. Individual gene segments differ between field strains of BTV; thus, we hypothesized that key viral genes undergo genetic drift during alternating passage of BTV in its ruminant and insect hosts. To test this hypothesis, variation in the consensus sequence and quasispecies heterogeneity of the VP2 and NS3/NS3A genes of a plaque-purified strain of BTV serotype 10 was determined during alternating infection of vector Culicoides sonorensis and a sheep and calf. Consensus sequences were determined after reverse transcriptase-nested PCR amplification of viral RNA directly from ruminant blood and homogenized insects, and quasispecies heterogeneity was determined by the sequencing of clones derived from directly amplified viral RNA. Comparison of these sequences to those of the original BTV inoculum used to initiate the cycle of BTV infection demonstrated, for the first time, that individual BTV gene segments evolve independently of one another by genetic drift in a host-specific fashion, generating quasispecies populations in both ruminant and insect hosts. Furthermore, a unique viral variant was randomly ingested by C. sonorensis insects that fed on a sheep with low-titer viremia, thereby fixing a novel genotype by founder effect. Thus, we conclude that genetic drift and founder effect contribute to diversification of individual gene segments of field strains of BTV.

  9. Confirmation of a founder effect in a Northern European population of a new β-globin variant: HBB:c.23_26dup (codons 8/9 (+AGAA))

    PubMed Central

    Marchi, Nina; Pissard, Serge; Cliquennois, Manuel; Vasseur, Christian; Le Metayer, Nathalie; Mereau, Claude; Jouet, Jean Pierre; Georgel, Anne-France; Genin, Emmanuelle; Rose, Christian

    2015-01-01

    β-Thalassemia is a genetic disease caused by a defect in the production of the β-like globin chain. More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites. We recently described a duplication of four nucleotides in the first exon of β-globin gene in several families of patients living in Nord-Pas-de-Calais (France). Using the genotypes at 12 microsatellite markers surrounding the β-globin gene of four unrelated variant carriers plus an additional one recently discovered, we found that they shared a common haplotype indicating a founder effect that was estimated to have taken place 225 years ago (nine generations). In order to determine whether this variant arose in this region of Northern Europe or was introduced by migrants from regions of the world where thalassemia is endemic, we genotyped the first 4 unrelated variant carriers and 32 controls from Nord-Pas-de-Calais for 97 European ancestry informative markers (EAIMs). Using these EAIMs and comparing with population reference panels, we demonstrated that the variant carriers were very similar to the controls and were closer to North European populations than to South European or Middle-East populations. Rare β-thalassemia variants have already been described in patients sampled in non-endemic regions, but it is the first proof of a founder effect in Northern Europe. PMID:25469539

  10. Confirmation of a founder effect in a Northern European population of a new β-globin variant: HBB:c.23_26dup (codons 8/9 (+AGAA)).

    PubMed

    Marchi, Nina; Pissard, Serge; Cliquennois, Manuel; Vasseur, Christian; Le Metayer, Nathalie; Mereau, Claude; Jouet, Jean Pierre; Georgel, Anne-France; Genin, Emmanuelle; Rose, Christian

    2015-09-01

    β-Thalassemia is a genetic disease caused by a defect in the production of the β-like globin chain. More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites. We recently described a duplication of four nucleotides in the first exon of β-globin gene in several families of patients living in Nord-Pas-de-Calais (France). Using the genotypes at 12 microsatellite markers surrounding the β-globin gene of four unrelated variant carriers plus an additional one recently discovered, we found that they shared a common haplotype indicating a founder effect that was estimated to have taken place 225 years ago (nine generations). In order to determine whether this variant arose in this region of Northern Europe or was introduced by migrants from regions of the world where thalassemia is endemic, we genotyped the first 4 unrelated variant carriers and 32 controls from Nord-Pas-de-Calais for 97 European ancestry informative markers (EAIMs). Using these EAIMs and comparing with population reference panels, we demonstrated that the variant carriers were very similar to the controls and were closer to North European populations than to South European or Middle-East populations. Rare β-thalassemia variants have already been described in patients sampled in non-endemic regions, but it is the first proof of a founder effect in Northern Europe. PMID:25469539

  11. Fine-Mapping the Wheat Snn1 Locus Conferring Sensitivity to the Parastagonospora nodorum Necrotrophic Effector SnTox1 Using an Eight Founder Multiparent Advanced Generation Inter-Cross Population

    PubMed Central

    Cockram, James; Scuderi, Alice; Barber, Toby; Furuki, Eiko; Gardner, Keith A.; Gosman, Nick; Kowalczyk, Radoslaw; Phan, Huyen P.; Rose, Gemma A.; Tan, Kar-Chun; Oliver, Richard P.; Mackay, Ian J.

    2015-01-01

    The necrotrophic fungus Parastagonospora nodorum is an important pathogen of one of the world’s most economically important cereal crops, wheat (Triticum aestivum L.). P. nodorum produces necrotrophic protein effectors that mediate host cell death, providing nutrients for continuation of the infection process. The recent discovery of pathogen effectors has revolutionized disease resistance breeding for necrotrophic diseases in crop species, allowing often complex genetic resistance mechanisms to be broken down into constituent parts. To date, three effectors have been identified in P. nodorum. Here we use the effector, SnTox1, to screen 642 progeny from an eight-parent multiparent advanced generation inter-cross (i.e., MAGIC) population, genotyped with a 90,000-feature single-nucleotide polymorphism array. The MAGIC founders showed a range of sensitivity to SnTox1, with transgressive segregation evident in the progeny. SnTox1 sensitivity showed high heritability, with quantitative trait locus analyses fine-mapping the Snn1 locus to the short arm of chromosome 1B. In addition, a previously undescribed SnTox1 sensitivity locus was identified on the long arm of chromosome 5A, termed here QSnn.niab-5A.1. The peak single-nucleotide polymorphism for the Snn1 locus was converted to the KASP genotyping platform, providing breeders and researchers a simple and cheap diagnostic marker for allelic state at Snn1. PMID:26416667

  12. Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) Founder Mutation: Clues from Haplotyping of Short Tandem Repeats on Chromosome 17p

    PubMed Central

    Paskulin, Diego Davila; Giacomazzi, Juliana; Achatz, Maria Isabel; Costa, Sandra; Reis, Rui Manoel; Hainaut, Pierre; dos Santos, Sidney Emanuel Batista; Ashton-Prolla, Patricia

    2015-01-01

    Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial history. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Iberic origin, distant in about 72–84 generations (2000 years assuming a 25 years intergenerational distance) and thus pre-dating European migration to Brazil. So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil. PMID:26618902

  13. 90-letnij yubilej osnovatelya IAI Petra Grigor'evicha Kulikovskogo %t The founder of "Studies in the history of astronomy" Dr. P. G. Kulikovsky: to his 90th birthday

    NASA Astrophysics Data System (ADS)

    Eremeeva, A. I.; Laerova, N. B.; Samus', N. N.

    On June 13, 2000, Moscow astronomers congratulated personally P. G. Kulikovsky, the renowned Russian astronomer and teacher of astronomy on his birthday. Born in Kiev in a family with noble Polish and French roots, he graduated from Moscow University in 1938 and worked at Sternberg Astronomical Institute and the Department of Astronomy of Moscow University. His main scientific interests are Galactic astronomy and history of astronomy. Kulikovsky was one of the pioneers of astronomical electrophotometry in the Soviet Union. He was most active in studies of variable stars, investigated connections of their statistical properties with those of the corresponding stars systems. Being a brilliant teacher, he lectured successfully on astronomical subjects in Moscow University. Friends also know him as a talented musician and composer, an author of many piano plays. Kulikovsky has done very much as an organizer of Soviet systematic researches on the history of astronomy. He is the author of many papers on the subject, the founder of the corresponding commission of the USSR Astronomical Council. Kulikovsky was an active member of the IAU, he served as President of the IAU Commission 41 (History of Astronomy) in 1958 - 1964.

  14. Arabidopsis poly(A) polymerase PAPS1 limits founder-cell recruitment to organ primordia and suppresses the salicylic acid-independent immune response downstream of EDS1/PAD4.

    PubMed

    Trost, Gerda; Vi, Son Lang; Czesnick, Hjördis; Lange, Peggy; Holton, Nick; Giavalisco, Patrick; Zipfel, Cyril; Kappel, Christian; Lenhard, Michael

    2014-03-01

    Polyadenylation of pre-mRNAs by poly(A) polymerase (PAPS) is a critical process in eukaryotic gene expression. As found in vertebrates, plant genomes encode several isoforms of canonical nuclear PAPS enzymes. In Arabidopsis thaliana these isoforms are functionally specialized, with PAPS1 affecting both organ growth and immune response, at least in part by the preferential polyadenylation of subsets of pre-mRNAs. Here, we demonstrate that the opposite effects of PAPS1 on leaf and flower growth reflect the different identities of these organs, and identify a role for PAPS1 in the elusive connection between organ identity and growth patterns. The overgrowth of paps1 mutant petals is due to increased recruitment of founder cells into early organ primordia, and suggests that PAPS1 activity plays unique roles in influencing organ growth. By contrast, the leaf phenotype of paps1 mutants is dominated by a constitutive immune response that leads to increased resistance to the biotrophic oomycete Hyaloperonospora arabidopsidis and reflects activation of the salicylic acid-independent signalling pathway downstream of ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)/PHYTOALEXIN DEFICIENT4 (PAD4). These findings provide an insight into the developmental and physiological basis of the functional specialization amongst plant PAPS isoforms.

  15. Metabolomic Assessment of Key Maize Resources: GC-MS and NMR Profiling of Grain from B73 Hybrids of the Nested Association Mapping (NAM) Founders and of Geographically Diverse Landraces.

    PubMed

    Venkatesh, Tyamagondlu V; Chassy, Alexander W; Fiehn, Oliver; Flint-Garcia, Sherry; Zeng, Qin; Skogerson, Kirsten; Harrigan, George G

    2016-03-16

    The present study expands metabolomic assessments of maize beyond commercial lines to include two sets of hybrids used extensively in the scientific community. One set included hybrids derived from the nested association mapping (NAM) founder lines, a collection of 25 inbreds selected on the basis of genetic diversity and used to investigate the genetic basis of complex plant traits. A second set included 24 hybrids derived from a collection of landraces representative of native diversity from North and South America that may serve as a source of new alleles for improving modern maize hybrids. Metabolomic analysis of grain harvested from these hybrids utilized gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) techniques. Results highlighted extensive metabolomic variation in grain from both hybrid sets, but also demonstrated that, within each hybrid set, subpopulations could be differentiated in a pattern consistent with the known genetic and compositional variation of these lines. Correlation analysis did not indicate a strong association of the metabolomic data with grain nutrient composition, although some metabolites did show moderately strong correlations with agronomic features such as plant and ear height. Overall, this study provides insights into the extensive metabolomic diversity associated with conventional maize germplasm. PMID:26923484

  16. Linkage disequilibrium at the Machado-Joseph disease spinal cerebellar ataxia 3 locus: Evidence for a common founder effect in French and Portuguese-Brazilian families as well as a second ancestral Portuguese-Azorean mutation

    SciTech Connect

    Stevanin, G.; Cancel, G.; Didierjean, O.

    1995-11-01

    Spinal cerebellar ataxia 3 (SCA3) is a genetic subtype of the type I autosomal dominant cerebellar ataxias (ADCA type I), a clinically and genetically heterogeneous group of neurological disorders. SCA3 was mapped in French families to chromosome 14q24.3-qter in the same region as the gene for Machado-Joseph disease (MJD), which was classified as a form of ADCA type I on the basis of similarities in the clinical presentation of individual patients. The MJD gene was recently identified in Japanese kindreds, and the mutation was characterized as an unstable CAG repeat that is expanded in affected individuals. The same mutation is observed in families of Portuguese-Azorean ancestry, as well as in French SCA3 kindreds. In other disorders caused by unstable and expanded triplet repeats, such as fragile X syndrome (FRA-X), myotonic dystrophy (MD), Huntington disease (HD), and SCA1, linkage disequilibrium (LD) between the mutation and closely linked polymorphic markers was detected, suggesting that there were only one or a few founders or predisposing haplotypes. In the present study, 29 families of different geographical origins were tested for LD between the MJD/SCA3 mutation and four flanking microsatellite markers. 27 refs., 2 tabs.

  17. High frequency and founder effect of the CYP3A4*20 loss-of-function allele in the Spanish population classifies CYP3A4 as a polymorphic enzyme.

    PubMed

    Apellániz-Ruiz, M; Inglada-Pérez, L; Naranjo, M E G; Sánchez, L; Mancikova, V; Currás-Freixes, M; de Cubas, A A; Comino-Méndez, I; Triki, S; Rebai, A; Rasool, M; Moya, G; Grazina, M; Opocher, G; Cascón, A; Taboada-Echalar, P; Ingelman-Sundberg, M; Carracedo, A; Robledo, M; Llerena, A; Rodríguez-Antona, C

    2015-06-01

    Cytochrome P450 3A4 (CYP3A4) is a key drug-metabolizing enzyme. Loss-of-function variants have been reported as rare events, and the first demonstration of a CYP3A4 protein lacking functional activity is caused by CYP3A4*20 allele. Here we characterized the world distribution and origin of CYP3A4*20 mutation. CYP3A4*20 was determined in more than 4000 individuals representing different populations, and haplotype analysis was performed using CYP3A polymorphisms and microsatellite markers. CYP3A4*20 allele was present in 1.2% of the Spanish population (up to 3.8% in specific regions), and all CYP3A4*20 carriers had a common haplotype. This is compatible with a Spanish founder effect and classifies CYP3A4 as a polymorphic enzyme. This constitutes the first description of a CYP3A4 loss-of-function variant with high frequency in a population. CYP3A4*20 results together with the key role of CYP3A4 in drug metabolism support screening for rare CYP3A4 functional alleles among subjects with adverse drug events in certain populations. PMID:25348618

  18. Contribution of the PALB2 c.2323C>T [p.Q775X] Founder mutation in well-defined breast and/or ovarian cancer families and unselected ovarian cancer cases of French Canadian descent

    PubMed Central

    2013-01-01

    Background The PALB2 c.2323C>T [p.Q775X] mutation has been reported in at least three breast cancer families and breast cancer cases of French Canadian descent and this has been attributed to common ancestors. The number of mutation-positive cases reported varied based on criteria of ascertainment of index cases tested. Although inherited PALB2 mutations are associated with increased risks of developing breast cancer, risk to ovarian cancer has not been fully explored in this demographically unique population. Methods We screened the PALB2 p.Q775X variant in 71 families with at least three cases of breast cancer (n=48) or breast and ovarian cancers (n=23) that have previously been found negative for at least the most common BRCA1 and BRCA2 mutations reported in the French Canadian population and in 491 women of French Canadian descent who had invasive ovarian cancer and/or low malignant potential tumors of the major histopathological subtypes. Results We identified a PALB2 p.Q775X carrier in a breast cancer family, who had invasive ductal breast carcinomas at 39 and 42 years of age. We also identified a PALB2 p.Q775X carrier who had papillary serous ovarian cystadenocarcinoma at age 58 among the 238 serous subtype ovarian cancer cases investigated, who also had breast cancer at age 52. Conclusion Our findings, taken together with previous reports, support adding PALB2 c.2323C>T p.Q775X to the list of cancer susceptibility genes for which founder mutations have been identified in the French Canadian population. PMID:23302520

  19. Robert Boyle: The Founder of Modern Chemistry

    NASA Astrophysics Data System (ADS)

    Williams, Kathryn R.

    2009-02-01

    When I learned that the 2009 Earth Day features "air", I started thinking about a suitable way to link the topic to past JCE issues. No small task, considering that I had already covered oxygen and nitrogen in the 2003 and 2005 Earth Day issues. So much for chemical composition. So, I turned to physical properties—the gas laws—that could equally be called the "air laws", since "air" was a generic word for a gas in the centuries when the laws were formulated. For Earth Day 2009, I focus on Robert Boyle, who discovered the first of the gas laws. In addition to at least 20 papers describing Boyle's Law demonstrations and experiments, The Honorable Robert Boyle (1627-1691) is the subject of five papers in JCE .

  20. Herbert Olivecrona: founder of Swedish neurosurgery.

    PubMed

    Ljunggren, B

    1993-01-01

    Herbert Olivecrona (1891-1980) singlehandedly founded Swedish neurosurgery. At the International Congress in Neurology in Bern in August, 1931, Harvey Cushing invited the cream of the world's medical society to a private banquet. Among the 28 specially invited guests was Herbert Olivecrona. At 40 years old, Olivecrona took his seat with pioneers such as Otfrid Foerster, Percival Bailey, Hugh Cairns, Geoffrey Jefferson, and Sir Charles Sherrington. This suggests that Cushing was impressed by the Swedish aristocrat's didactic deeds when he visited the Serafimer Hospital in Stockholm 2 years earlier. During the mid-1920's, the radiologist Erik Lysholm greatly improved the technique of ventriculography and, challenged by Olivecrona, his diagnostic neuroradiology became of superior quality. In the early 1930's, utilizing technical innovations of his own, Lysholm became a master at demonstrating and localizing posterior fossa tumors, which Olivecrona then operated on. Olivecrona's clinic became the mecca to which many scholars, thirsting for more knowledge, went on a pilgrimage. The international reputation of the clinic was founded, not on epoch-making discoveries, but by the resolute and practical application of methods already launched elsewhere and the exemplary organization that Olivecrona had established in collaboration with Lysholm. In spite of hardships and primitive working conditions, the clinic at the Serafimer Hospital gradually developed into the ideal prototype for a modern neurosurgical department. Olivecrona trained many colorful personalities who later were to lay the foundation for neurosurgery in their home countries; these included Wilhelm Tönnis of Germany, Edvard Busch of Denmark, and Aarno Snellman of Finland. Olivecrona was a true pioneer who made major contributions in practically all fields of conventional neurosurgery.

  1. Founders of fish culture - European origins

    USGS Publications Warehouse

    Fish, F.F.

    1936-01-01

    Just where true fish culture appeared in history depends entirely upon what one considers fish culture to be. If the transportation of fishes from regions of plenty to those of few is to be regarded as fish culture - as it is by some even today - then this story should start in remotest antiquity and deal with an amazing series of failures. However, fish culture to be classed as a science must include far more than mere transportation, it must include a deliberate effort on the part of man to master a technique of fish raising which will yield results far superior to Nature's. Accordingly, the wheel of history must be spun forward to the fifteenth century, A. D., when man first conceived the idea that with care and exactitude, he could improve upon Nature. The fish cultural efforts of the Chinese, the Egyptians, the Greeks, and the Romans may be skipped over in a hurry, for they represented little more than the transportation and rearing of wild fish. With the renaissance of modern civilization in Europe came the birth of scientific fish culture.

  2. Founder lines for improved citrus biotechnology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article discusses the research needed to develop the RMCE strategy and molecular assays for site-specific recombinases as tools for genome manipulation. Explanation of genetic engineering used to generate transgenic citrus plants to exhibit a novel phenotype, but not to contain the recombinase...

  3. Role of arc magmatism and lower crustal foundering in controlling elevation history of the Nevadaplano and Colorado Plateau: A case study of pyroxenitic lower crust from central Arizona, USA

    NASA Astrophysics Data System (ADS)

    Erdman, Monica E.; Lee, Cin-Ty A.; Levander, Alan; Jiang, Hehe

    2016-04-01

    Garnet-pyroxenite xenoliths from a 25 Ma volcano on the southern edge of the Colorado Plateau in central Arizona (USA) are shown here to have crystallized as deep-seated cumulates from hydrous arc magmas, requiring the generation of a large complement of felsic magmas. U-Pb dating of primary titanite grains indicates that crystallization probably occurred around 60 Ma. These observations suggest that voluminous arc magmatism reached as far inland as the edge of the Colorado Plateau during the Laramide orogeny. Here, we employ a combination of petrology, petrophysics, and seismic imaging to show that the formation and subsequent removal of a thick, dense, cumulate root beneath the ancient North American Nevadaplano modified the buoyancy of the orogenic plateau, possibly resulting in two uplift events. A late Cretaceous-early Tertiary uplift event should have occurred in conjunction with thickening of the crust by felsic magmatism. Additional uplift is predicted if the pyroxenite root later foundered, but such uplift must have occurred after ∼25 Ma, the age of the xenolith host. We show that seismic velocity anomalies and seismic structures in the central part of the Colorado Plateau could represent pyroxenitic layers that still reside there. However, under the southern and western margins of the Colorado Plateau, the seismic signatures of a pyroxenite root are missing, despite xenolith records and geochemical evidence for their existence prior to 25 Ma. We suggest that these particular regions have undergone recent removal of the pyroxenite root, leading to late uplift of the plateau. In summary, our observations suggest that the Nevadaplano, west of the Colorado Plateau and now represented by the Basin and Range province, was underlain by high elevations in the late Cretaceous through early Tertiary due to magmatic thickening. This may have facilitated an east-directed drainage pattern at this time. Subsequent collapse of the Nevadaplano, culminating in Basin and

  4. Transmitted/Founder and Chronic Subtype C HIV-1 Use CD4 and CCR5 Receptors with Equal Efficiency and Are Not Inhibited by Blocking the Integrin α4β7

    PubMed Central

    Banks, Lauren B.; Iyer, Shilpa S.; Pfaff, Jennifer M.; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Decker, Julie M.; Parrish, Erica H.; Berg, Anna; Hopper, Jennifer; Hora, Bhavna; Kumar, Amit; Mahlokozera, Tatenda; Yuan, Sally; Coleman, Charl; Vermeulen, Marion; Ding, Haitao; Ochsenbauer, Christina; Tilton, John C.; Permar, Sallie R.; Kappes, John C.; Betts, Michael R.; Busch, Michael P.; Gao, Feng; Montefiori, David; Haynes, Barton F.; Shaw, George M.; Hahn, Beatrice H.; Doms, Robert W.

    2012-01-01

    Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently. PMID:22693444

  5. Distal Limits and Composition of a Late Ordovician (Mohawkian) Biotite-Bearing Volcanic ash, Foreland Carbonate Platform (Verulam Formation), Ottawa Embayment: Helping to Define Magmatic Change in Volcanism Following Later Platform Foundering

    NASA Astrophysics Data System (ADS)

    Al-Delami, M.; Dix, G. R.

    2009-05-01

    burial temperatures of 130oC, in keeping with burial temperature estimates according to conodont alteration indices (CAI = 3) for the host carbonate platform succession. The MgO and FeO % of biotites from these beds plot within the same field as the slightly older Millbrig and Deike bentonites that also represent ash deposition within shallow-water carbonate platform environments from widespread Late Ordovician eruptions that occurred along the foreland basin margin. Collectively, these compositions are higher in FeO and lower in MgO % values compared those associated with a bentonite within the overlying Taconic foreland shale succession of the Ottawa Embayment, and bentonites in Lower Silurian successions of western Europe. This contrast strengthens a previous hypothesis (Sharma et al., 2005) that there was significant change in magmatic composition along the Taconic arc following or coincident with foundering of the foreland carbonate platform.

  6. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women.

    PubMed Central

    Abeliovich, D; Kaduri, L; Lerer, I; Weinberg, N; Amir, G; Sagi, M; Zlotogora, J; Heching, N; Peretz, T

    1997-01-01

    The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations. Images Figure 2 Figure 3 PMID:9042909

  7. The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women

    SciTech Connect

    Abeliovich, D.; Lerer, I.; Weinberg, N.

    1997-03-01

    The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations. 25 refs., 3 figs., 6 tabs.

  8. [Max Hirsch founder of rheumatology in Germany: banished and murdered].

    PubMed

    Keitel, W

    2014-08-01

    The Jewish physician and scientist Dr. Max Hirsch (1875-1941) made a substantial contribution to consolidation of the foundations of his professional discipline, balneology, and in particular developed the social aspects. He recognized the economic significance of diseases of the musculoskeletal system very early on and gathered important ideas from abroad. Together with the department head in the Prussian Ministry of Education and Cultural Affairs, the Privy Councillor Prof. Dr. Eduard Dietrich and later alone, he was editor of various balneological journals. He worked as general secretary of the Deutsche Gesellschaft für Rheumatologie (German Society of Rheumatology) from the beginning of its existence (1927) and created the publication series Veröffentlichungen der Deutschen Gesellschaft für Rheumabekämpfung (Publications of the German Society against Rheumatism) and Rheuma-Jahrbuch (Annual review of rheumatology) in 1929, 1930 and 1931 and organized seven rheumatology congresses up to 1933. After the accession to power of the National Socialists, Max Hirsch and Eduard Dietrich were deposed from office. Hirsch emigrated to Latvia via Switzerland and the Soviet Union with his wife and one son where they were murdered in the course of the Jewish pogrom. The second son escaped with his family to Sweden. PMID:24599355

  9. [Max Hirsch founder of rheumatology in Germany: banished and murdered].

    PubMed

    Keitel, W

    2014-08-01

    The Jewish physician and scientist Dr. Max Hirsch (1875-1941) made a substantial contribution to consolidation of the foundations of his professional discipline, balneology, and in particular developed the social aspects. He recognized the economic significance of diseases of the musculoskeletal system very early on and gathered important ideas from abroad. Together with the department head in the Prussian Ministry of Education and Cultural Affairs, the Privy Councillor Prof. Dr. Eduard Dietrich and later alone, he was editor of various balneological journals. He worked as general secretary of the Deutsche Gesellschaft für Rheumatologie (German Society of Rheumatology) from the beginning of its existence (1927) and created the publication series Veröffentlichungen der Deutschen Gesellschaft für Rheumabekämpfung (Publications of the German Society against Rheumatism) and Rheuma-Jahrbuch (Annual review of rheumatology) in 1929, 1930 and 1931 and organized seven rheumatology congresses up to 1933. After the accession to power of the National Socialists, Max Hirsch and Eduard Dietrich were deposed from office. Hirsch emigrated to Latvia via Switzerland and the Soviet Union with his wife and one son where they were murdered in the course of the Jewish pogrom. The second son escaped with his family to Sweden.

  10. The founder of Vicks: Lunsford Richardson (1854-1919).

    PubMed

    Al Aboud, Khalid

    2010-01-01

    Vicks VapoRub (Procter & Gamble, Cincinnati, OH) is one of the most popular over-the-counter therapies in the world, used to provide relief from the symptoms of the common cold and non-life-threatening respiratory infections. Even as more advanced products have come and gone, VapoRub continues to dominate the market almost 9 decades after the death of its formulator, Lunsford Richardson (Figure).

  11. [Charles Robert Darwin: the great founder of scientific evolutionism].

    PubMed

    Liang, Qian-Jin; Bin, Jie; Zhang, Gen-Fa

    2009-12-01

    Today, we celebrated 200 years since Charles Darwin, one of the world's most creative and influential thinkers, was born. And there happens to be the 150th anniversary of the publication of his famous book, On the Origin of Species. It is verified that On the Origin of Species is an immortal classic book and is still guiding the study of anagenesis in life science as the development of natural science from then on, and even though most of the ideas in the book are well-known at the present age. In the article, we recall the brilliance and predomination life of Darwin, a great sage with rich scientific achievements, review briefly the novel discoveries and theories after him in the field, and then elucidate the focal points and perspectiveas in near future study of evolution. PMID:20042383

  12. Renal denervation for hypertension: observations and predictions of a founder.

    PubMed

    Esler, Murray

    2014-05-01

    The 6-year anniversary of the first catheter-based renal denervation procedure for resistant hypertension has passed, and the 3-year follow-up results of the Symplicity HTN-1 are now published. At the 'end of the beginning', it is timely to reflect on the observations to-date for this revolutionary therapy, and to predict the next phase in its development and clinical application in hypertension treatment. In essence, on observations to hand, the procedure is efficacious and seems safe and durable. But will the blood pressure lowering truly be permanent (or might it be cancelled out by renal sympathetic nerve regrowth)? How can patient selection for the renal denervation procedure be optimized, given that some patients do not respond with a blood pressure fall? Will blood pressure lowering with renal denervation reduce the rate of clinical cardiovascular endpoints? Will long-term safety be acceptable? Can milder hypertension be cured? And there are unresolved procedural and technical questions: how much renal denervation is optimal; is unilateral denervation, now commonly used, beneficial; will renal denervation show a 'class effect', with the different energy forms now used for renal nerve ablation producing equivalent blood pressure lowering? At the 12-year anniversary, I expect these questions will be answered, and catheter-based renal denervation will have an established clinical role in the care of patients with severe grades of hypertension. Less certain is the common prediction of its application in early, mild hypertension, in parallel with, or even before anti-hypertensive drug prescribing.

  13. Far above rubies: the founders of Every Child By Two.

    PubMed

    Wiederhorn, N

    1992-01-01

    The Every Child By Two Campaign was formed by Rosalynn Carter and Betty Bumpers, spouses of prominent elected officials, in response to the rapid increase in measles cases in the United States in 1990. They have sought to create a network of community leaders that will act to get children immunized now and will influence legislation to ensure that children under two will be fully immunized in the future.

  14. Foundering lithosphere imaged beneath the southern Sierra Nevada, California, USA.

    PubMed

    Boyd, Oliver S; Jones, Craig H; Sheehan, Anne F

    2004-07-30

    Seismic tomography reveals garnet-rich crust and mantle lithosphere descending into the upper mantle beneath the southeastern Sierra Nevada. The descending lithosphere consists of two layers: an iron-rich eclogite above a magnesium-rich garnet peridotite. These results place descending eclogite above and east of high P wave speed material previously imaged beneath the southern Great Valley, suggesting a previously unsuspected coherence in the lithospheric removal process. PMID:15286370

  15. [Chin Junso--founder of the medical lineage Uirou].

    PubMed

    Sugiyama, Shigeru

    2002-01-01

    Chin Junso was an excellent doctor with expertise in the medical sciences gained from teachings that originated in the Kin and Gen dynasties. He devised and used unique prescriptions with various aromatics, which he collectively called Hoyaku (fragrant medication). Although he did not desire to enter government service because of his old age, his knowledge and wishes were handed down to his descendants. He led a quiet life in his later years by practicing meditation at a Zen temple of the Rinzai-shu order. Uirou in Odawara incidentally belongs to the Nichiren-shu order and not to the lineage of Junso. Nichiren-shu was a Buddhism order popular among townspeople in Kyoto at that time. It may be of interest to note the second master Souju and the third master Jouyu contributed to the trade between Japan and Korea.

  16. Wolfgang Schott (1905-1989): the founder of quantitative paleoceanography

    NASA Astrophysics Data System (ADS)

    Dullo, Wolf-Christian; Pfaffl, Fritz A.

    2016-06-01

    Wolfgang Schott is the pioneer in paleoceanography and has established this research field within marine geology. His papers from the first half of the twentieth century are all published in German; therefore, the most inspiring results are given here as original quotes in English, since they paved the ground for all scientific discussions on climate stratigraphy, past ocean currents, and glacial interglacial cycles.

  17. Far above rubies: the founders of Every Child By Two.

    PubMed

    Wiederhorn, N

    1992-01-01

    The Every Child By Two Campaign was formed by Rosalynn Carter and Betty Bumpers, spouses of prominent elected officials, in response to the rapid increase in measles cases in the United States in 1990. They have sought to create a network of community leaders that will act to get children immunized now and will influence legislation to ensure that children under two will be fully immunized in the future. PMID:1408425

  18. Gregor Mendel, OSA (1822-1884), founder of scientific genetics.

    PubMed

    Dunn, P M

    2003-11-01

    Gregor Mendel, an Augustinian monk and part-time school teacher, undertook a series of brilliant hybridisation experiments with garden peas between 1857 and 1864 in the monastery gardens and, using statistical methods for the first time in biology, established the laws of heredity, thereby establishing the discipline of genetics.

  19. [Baron Dominique-Jean Larrey: the founder of urological traumatology].

    PubMed

    Hatzinger, M; Ameijenda, C; Lent, V; Sohn, M

    2012-12-01

    Dominique-Jean Larrey (1766-1842) was Surgeon-in-Chief of the Grande Army under Napoleon Bonaparte (1769-1821) and personal physician of the Emperor. Against the opposition of the traditionalists he introduced the "ambulances volantes", the so-called flying ambulances. The aim was the medical treatment of the injured soldiers immediately on the battlefield. This revolutionary treatment led to a benefit not only for the own soldiers, but also for the wounded enemies. His innovation in the field of immediate assistance of wounded persons, together with Larreys' outstanding medical competence, saved thousands of soldiers lives on the battlefield of the Napoleonic wars. His memories concerning the military campaigns, have been even up to the 20th century one of the standard works of modern military surgery. He had as well great interest in urolological injuries of the urinary system and their conservative and operative care. Up to these days, his work shows a surprising actuality and perfect anatomic understanding. In a time without anaesthetics, antibiotics and under primitive circumstances, Larrey and his collegues accomplished surgical feats. Larreys flying ambulances were copied by many different countries. The American Mobile Army Surgical Hospital (M.A.S.H) is clearly based on his thoughts and ideals. In our opinion he is the father of the modern war surgery as well the urological traumatology. PMID:23254353

  20. Platte pipe line, built in 50s, exceeded founders' dreams

    SciTech Connect

    Not Available

    1984-05-01

    This is a short paper on the history and development of the Platte Pipe Line which stretches 1156 miles from Byron, Wyoming, to Wood River, Illinois. It discusses the development and significance of one of the most used crude oil pipelines in the United States. It also discusses its role in advanced pipeline control technology and the future of the system.

  1. Rejuvenating a foundering institutional review board: one institution's story.

    PubMed

    De Ville, Kenneth; Hassler, Gregory; Lewis, Michael J

    2007-01-01

    This report recounts one institution's experience in the fundamental reorganization of its institutional review board (IRB). With an appropriate approach, organizational structure, and ethos, the goals of research participant safety, regulatory compliance, and efficiency are not in conflict but, rather, mutually reinforcing. These important goals were realized because all aspects of the IRB reorganization were guided by and measured against five related principles: (1) expertise, (2) service, (3) credibility, (4) efficiency, and (5) accountability. This medium-sized academic IRB was successfully reorganized to increase the scrutiny of protection of human subjects and to promote efficiency and investigator services. On average, the office returned expedited submissions to investigators with approvals or queries within two working days of submission. On submissions requiring full committee review, letters and faxes were issued to investigators within 48 hours of committee meetings. This turnaround time (combined with a nine-day premeeting submission requirement) meant that investigators who had submitted new studies for full committee review received an approval, request for modifications, queries for more information, or disapproval within 11 days from the reorganized IRB. In contrast, an Office of the Inspector General study noted that IRBs in academic medical centers typically report decisions within an average of 37 days. The reforms included mechanical and operational changes within office procedure, a robust educational program for committee members, and a revamped IRB office staff that decreased the total number of office employees from five to four but that increased educational levels and skills of the staff members.

  2. [Baron Dominique-Jean Larrey: the founder of urological traumatology].

    PubMed

    Hatzinger, M; Ameijenda, C; Lent, V; Sohn, M

    2012-12-01

    Dominique-Jean Larrey (1766-1842) was Surgeon-in-Chief of the Grande Army under Napoleon Bonaparte (1769-1821) and personal physician of the Emperor. Against the opposition of the traditionalists he introduced the "ambulances volantes", the so-called flying ambulances. The aim was the medical treatment of the injured soldiers immediately on the battlefield. This revolutionary treatment led to a benefit not only for the own soldiers, but also for the wounded enemies. His innovation in the field of immediate assistance of wounded persons, together with Larreys' outstanding medical competence, saved thousands of soldiers lives on the battlefield of the Napoleonic wars. His memories concerning the military campaigns, have been even up to the 20th century one of the standard works of modern military surgery. He had as well great interest in urolological injuries of the urinary system and their conservative and operative care. Up to these days, his work shows a surprising actuality and perfect anatomic understanding. In a time without anaesthetics, antibiotics and under primitive circumstances, Larrey and his collegues accomplished surgical feats. Larreys flying ambulances were copied by many different countries. The American Mobile Army Surgical Hospital (M.A.S.H) is clearly based on his thoughts and ideals. In our opinion he is the father of the modern war surgery as well the urological traumatology.

  3. Satyendranath Bose: Co-Founder of Quantum Statistics

    ERIC Educational Resources Information Center

    Blanpied, William A.

    1972-01-01

    Satyendranath Bose was first to prove Planck's Law by using ideal quantum gas. Einstein credited Bose for this first step in the development of quantum statistical mechanics. Bose did not realize the importance of his work, perhaps because of peculiar academic settings in India under British rule. (PS)

  4. [Tibor Péterfi, the founder of micromanipulation].

    PubMed

    Donáth, Tibor

    2010-01-01

    Tibor Péterfi (1883-1953) was an eminent and internationally renowned biologist. He made great advances in the field of experimental physiology focusing his cytological research on microscopic examination of living cells. For this task, he created a tool named micromanipulator basing the development of microsurgery and that of cell surgery as well. His histological and cytological researches took their beginning first in Kolozsvár/Cluj (then Hungary, now Romania), where he worked as an assistant of professor István Apáthy then in Budapest where he spent fruitful years under the tutorship of professor Mihály Lenhossék. His scientific career however was broken by the political persecution which followed the fall of the communist revolution in 1919. He emigrated and spent the following decades in Prague, in Jena, in Berlin and in Cambridge. The apogee however of his scientific career proved to be the period he spent in Istanbul as a guest professor of the local university. He returned home only after the war already mortally ill. His illness did not allow him to continue his activity any more. Present article evaluates Tibor Péterfi's scientific achievements based mostly on recent archival researches.

  5. Foundering lithosphere imaged beneath the southern Sierra Nevada, California, USA.

    PubMed

    Boyd, Oliver S; Jones, Craig H; Sheehan, Anne F

    2004-07-30

    Seismic tomography reveals garnet-rich crust and mantle lithosphere descending into the upper mantle beneath the southeastern Sierra Nevada. The descending lithosphere consists of two layers: an iron-rich eclogite above a magnesium-rich garnet peridotite. These results place descending eclogite above and east of high P wave speed material previously imaged beneath the southern Great Valley, suggesting a previously unsuspected coherence in the lithospheric removal process.

  6. [Charles Robert Darwin: the great founder of scientific evolutionism].

    PubMed

    Liang, Qian-Jin; Bin, Jie; Zhang, Gen-Fa

    2009-12-01

    Today, we celebrated 200 years since Charles Darwin, one of the world's most creative and influential thinkers, was born. And there happens to be the 150th anniversary of the publication of his famous book, On the Origin of Species. It is verified that On the Origin of Species is an immortal classic book and is still guiding the study of anagenesis in life science as the development of natural science from then on, and even though most of the ideas in the book are well-known at the present age. In the article, we recall the brilliance and predomination life of Darwin, a great sage with rich scientific achievements, review briefly the novel discoveries and theories after him in the field, and then elucidate the focal points and perspectiveas in near future study of evolution.

  7. [ELIE METCHNIKOFF--THE FOUNDER OF LONGEVITY SCIENCE AND A FOUNDER OF MODERN MEDICINE: IN HONOR OF THE 170TH ANNIVERSARY].

    PubMed

    Stambler, I S

    2015-01-01

    The years 2015-2016 mark a double anniversary--the 170th anniversary of birth and the 100th anni- versary of death--of one of the greatest Russian scientists, a person that may be considered a founding figure of modern immunology, aging and longevity science--Elie Metchnikoff (May 15, 1845-July 15, 1916). At this time of the rapid aging of the world population and the rapid development of technologies that may ameliorate degenerative aging processes, Metchnikoff's pioneering contribution to the search for anti-aging and healthspan-extending means needs to be recalled and honored.

  8. James Smithson (1765-1829): Smithsonian Institution Founder And Its First Meteorite Investigator

    NASA Astrophysics Data System (ADS)

    Clarke, R. S., Jr.; Ewing, H. P.

    2005-12-01

    The Englishman James Smithson's bequest led to the founding of the Smithsonian Institution in Washington in 1846. He had never visited the US and his motivations are unclear. His archive and meteorite-containing mineral collection were also donated but were tragically lost in the Smithsonian fire in 1865. Only a tantalizing quotation remains: "the cabinet also contained a valuable suite of meteoritic stones, which appear to be . . . the important meteorites which have fallen in Europe during several centuries." Smithson's life spanned late 18th century Enlightenment skepticism concerning meteorites to their acceptance in the early decades of the 19th century. New research reveals Smithson as an active participant at the birth of modern meteoritics. Smithson was well educated, well connected, financially independent, and one of the youngest men ever to be elected a FRS. He spent much of his life in Europe associating with the scientific leaders there, and he was a sought after chemical analyst. William Thomson (1761-1806), an Oxford mentor and a lifelong friend, took up residence in Naples in 1790. He was monitoring Mt. Vesuvius's, an interest shared with Smithson, when it erupted on June 15, 1794. The next day the Siena meteorite fell 200 km to the north. Smithson, then residing in Florence, went immediately over the Chianti Hills to investigate the fall. Welcomed with awed respect by the local savants, the twenty nine year old Smithson investigated the fall and described it in a letter to his mentor Henry Cavendish (1731-1810) for dissemination in London. William Thomson provided a mineralogical description of the Siena stones for the published description. The Siena meteorite fall marked the beginning of a decade of investigation by scientists that led to the acceptance of meteorites. Smithson was there throughout these investigations and the political and social unrest that accompanied them.

  9. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects

    PubMed Central

    Schaffner, Adam; Fedick, Anastasia; Kaye, Lauren E.; Liao, Jun; Yachelevich, Naomi; Chu, Mary-Lynn; Boles, Richard G.; Moran, Ellen; Tokita, Mari; Gorman, Elizabeth; Zhang, Wei; Xia, Fan; Leduc, Magalie; Yang, Yaping; Eng, Christine; Wong, Lee-Jun; Schiffmann, Raphael; Diaz, George A.; Kornreich, Ruth; Thummel, Ryan; Wasserstein, Melissa; Yue, Zhenyu; Edelmann, Lisa

    2016-01-01

    Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway. PMID:27120463

  10. Founder of systems chemistry and foundational theoretical biologist: Tibor Gánti (1933-2009).

    PubMed

    Szathmáry, Eörs

    2015-09-21

    With his chemoton theory theoretical biologist and chemical engineer Tibor Gánti was one of the most outstanding intellects behind systems chemistry and the at the foundations of theoretical biology. A brief review of his oeuvre is presented. This essay introduces a special issue dedicated to his memory. PMID:25957522

  11. [Volodymyr Petrovych Vendt--a founder of sceintific trends in photobiochemistry and biotechnology in Ukraine].

    PubMed

    2006-01-01

    Professor Volodymyr Petrovych Vendt (30.11.1906, Kremenchug, Ukraine-22.11.1997, Kyiv, Ukraine), Doctor of science (biol.), Laureate of the State Prize of Ukraine graduated from the Odessa Physico-Pharmaceutical Institute (1930) in speciality chemist-analyst and was assigned to work at the Ukrainian Institute of Pathology and Labour Hygiene in Kharkiv. He was soon taken on as a scientific worker at the Ukrainian Institute of Experimental Medicine. He defended his thesis for the Candidate's degree and acquired the academic status of the senior scientific worker in 1939, and that of docent (assistant professor) in 1940. In 1938-1941 Volodymyr Petrovych read lectures at the Department of Chemistry of the Academy of Service Corps of the Workers' and Peasants' Red Army. At that time his scientific interests were connected with development of simple express-methods for detecting various substances, including chemical weed- and pest-killers which were used in agriculture. In 1944-1946 V. P. Vendt took part in military operations at the 1st Ukrainian Front, and after the release he was taken on as the senior scientific worker at the Institute of Biochemistry of the Academy of Sciences of the Ukrainian SSR, where he worked during 47 years. In 1961, after defending the thesis for the Doctor's degree Volodymyr Petrovych acquired the academic status of professor. In 1963 V. P. Vendt became a head of the Laboratory and then (1966) - of the Deaprtment of Photobiochemistry and from 1976 to 1983 - the Department of Sterol Biochemistry. He was the first to make the broad-scale investigations of sterol biochemistry, first of all group D vitamins, and came close to finding out the action mechanism of vitamin D3 - cholecalciferol. V. P. Vendt was one of the first to show a possibility of formation of sterene complexes with proteins and to find out the nature of chemical relations between them. That made it possible to develop the methods of obtaining artificial protein-vitamin complexes of high activity on the basis of casein (or other proteins) with preparations of vitamins D2, D3, E, carotene. Vitamin industry of the USSR used the technology, elaborated by V. P. Vendt, for the industrial production of vitamin D3 (videin D3) for poultry farming and medicine. He offered the method of early diagnosis of D-hypovitaminosis in chickens and developed and put into medical practice the methods of early diagnosis of rachitis in children and the degree of the disease risk by the umbilical blood analysis. V. P. Vendt and R. I. Yakhymovych were the first to obtain crystalline vitamin D3 and its complex with cholesterol (videchol) which was successfully used for rachitis prophylaxis and therapy in children. V. P. Vendt is the author of above 200 scientific works, 17 author's certificates and inventions. The scientific school of V. P. Vendt numbers 4 doctors and 16 candidates of science and above 60 research workers. The selfless work of the scientist was marked by state awards--by six medals and the State Prize of Ukraine in the field of science and technology "For investigations in vitamin D chemistry and biochemistry, creation of industrial technology of its production and introduction into medicine and agriculture" (jointly with R. I. Yakhymovych).

  12. [Zheng Yu-lin, a founder of the acupuncture and moxibustion cause of new China].

    PubMed

    Tian, Da-zhe; Liu, Jun-chi; Zhao, Juan; Zheng, Jun-jiang

    2007-07-01

    Mr. ZHENG Yu-lin is one of the most outstanding acupuncture scientists in the modern times in our country. He inherits the learning handed down in a family and is bold in making innovations, successfully combines the exercises to benefit the internal organs with Chinese traditional acupuncture needling methods, forming a set of unique Zheng's needling methods, which is used for treatment of severe ophthalmopathy with excellent therapeutic effects, and is famed the world over. Main achievements: took on scientific researches of acupuncture and moxibustion, teaching and clinical works in the first stage of establishment of China Academy of Traditional Chinese Medicinel trains a large number of famous specificities of acupuncture and moxibustion for new China; advocates study on channel essence; cures stubborn diseases for leaders of friend countries undertaking the great trust of the central leaders for many times, becoming an important ties of Chinese political foreign affairs. PMID:17722840

  13. Molecular epidemiology of O139 Vibrio cholerae: mutation, lateral gene transfer, and founder flush.

    PubMed

    Garg, Pallavi; Aydanian, Antonia; Smith, David; J Glenn, Morris; Nair, G Balakrish; Stine, O Colin

    2003-07-01

    Vibrio cholerae in O-group 139 was first isolated in 1992 and by 1993 had been found throughout the Indian subcontinent. This epidemic expansion probably resulted from a single source after a lateral gene transfer (LGT) event that changed the serotype of an epidemic V. cholerae O1 El Tor strain to O139. However, some studies found substantial genetic diversity, perhaps caused by multiple origins. To further explore the relatedness of O139 strains, we analyzed nine sequenced loci from 96 isolates from patients at the Infectious Diseases Hospital, Calcutta, from 1992 to 2000. We found 64 novel alleles distributed among 51 sequence types. LGT events produced three times the number of nucleotide changes compared to mutation. In contrast to the traditional concept of epidemic spread of a homogeneous clone, the establishment of variant alleles generated by LGT during the rapid expansion of a clonal bacterial population may be a paradigm in infections and epidemics. PMID:12890320

  14. A New Molecular Platform for Authentic Transmitted/Founder Viruses | Poster

    Cancer.gov

    In the past, nonhuman primate research has relied on only a few infectious molecular clones for numerous diverse research projects including pathogenesis, preclinical vaccine evaluations, transmissions, and host vs. pathogen interactions. But new data suggests that there is a selected phenotype of the simian immunodeficiency virus (SIV) that causes infection.

  15. Sister Mary Emil Penet, I.H.M.: Founder of the Sister Formation Conference

    ERIC Educational Resources Information Center

    Glisky, Joan

    2006-01-01

    Mary Emil Penet, I.H.M., (1916-2001) used her talents and charisma to shape the first national organization of American women religious, the Sister Formation Conference (SFC; 1954-1964), facilitating the integrated intellectual, spiritual, psychological, and professional development of vowed women religious. In the decade preceding Vatican II, her…

  16. John Warren (1753-1815): American surgeon, patriot and Harvard Medical School founder.

    PubMed

    Craig, Stephen C

    2010-08-01

    Dr John Warren was educated in the medical apprenticeship tradition of mid-18th century Boston, Massachusetts. As a surgeon in the American Continental Army he honed not only his surgical but also his teaching skills by providing continuing medical education to his colleagues in Boston's military hospital. Warren became a driving force in post-war Boston medicine. His organizational talents, zeal for science and vision for Massachusetts medicine led to the creation of Harvard Medical School.

  17. Multiple Local and Recent Founder Effects of TGM1 in Spanish Families

    PubMed Central

    Fachal, Laura; Rodríguez-Pazos, Laura; Ginarte, Manuel; Toribio, Jaime; Salas, Antonio; Vega, Ana

    2012-01-01

    Background Mutations in the TGM1 gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all TGM1 gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region. Methodology/Principal Findings In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the TGM1 gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry. Conclusions/Significance In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on TGM1 haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth. PMID:22511925

  18. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects.

    PubMed

    Zhang, Jinglan; Lachance, Véronik; Schaffner, Adam; Li, Xianting; Fedick, Anastasia; Kaye, Lauren E; Liao, Jun; Rosenfeld, Jill; Yachelevich, Naomi; Chu, Mary-Lynn; Mitchell, Wendy G; Boles, Richard G; Moran, Ellen; Tokita, Mari; Gorman, Elizabeth; Bagley, Kaytee; Zhang, Wei; Xia, Fan; Leduc, Magalie; Yang, Yaping; Eng, Christine; Wong, Lee-Jun; Schiffmann, Raphael; Diaz, George A; Kornreich, Ruth; Thummel, Ryan; Wasserstein, Melissa; Yue, Zhenyu; Edelmann, Lisa

    2016-04-01

    Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway. PMID:27120463

  19. Evidence of Long-Lived Founder Virus in Mother-to-Child HIV Transmission

    PubMed Central

    Danaviah, Sivapragashini; de Oliveira, Tulio; Bland, Ruth; Viljoen, Johannes; Pillay, Sureshnee; Tuaillon, Edouard; Van de Perre, Philippe; Newell, Marie-Louise

    2015-01-01

    Exposure of the infant’s gut to cell-associated and cell-free HIV-1 trafficking in breast milk (BM) remains a primary cause of mother-to-child transmission (MTCT). The mammary gland represents a unique environment for HIV-1 replication and host-virus interplay. We aimed to explore the origin of the virus transmitted during breastfeeding, and the link with quasi-species found in acellular and cellular fractions of breast-milk (BM) and in maternal plasma. The C2–V5 region of the env gene was amplified, cloned and sequenced from the RNA and DNA of BM, the RNA from the mother’s plasma (PLA) and the DNA from infant’s dried blood spot (DBS) in 11 post-natal mother-infant pairs. Sequences were assembled in Geneious, aligned in ClustalX, manually edited in SeAL and phylogenetic reconstruction was undertaken in PhyML and MrBayes. We estimated the timing of transmission (ETT) and reconstructed the time for the most recent common ancestor (TMRCA) of the infant in BEAST. Transmission of single quasi-species was observed in 9 of 11 cases. Phylogenetic analysis illustrated a BM transmission event by cell-free virus in 4 cases, and by cell-associated virus in 2 cases but could not be identified in the remaining 5 cases. Molecular clock estimates, of the infant ETT and TMRCA, corresponded well with the timing of transmission estimated by sequential infant DNA PCR in 10 of 11 children. The TMRCA of BM variants were estimated to emerge during gestation in 8 cases. We hypothesize that in the remaining cases, the breast was seeded with a long-lived lineage latently infecting resting T-cells. Our analysis illustrated the role of DNA and RNA virus in MTCT. We postulate that DNA archived viruses stem from latently infected quiescent T-cells within breast tissue and MTCT can be expected to continue, albeit at low levels, should interventions not effectively target these cells. PMID:25793402

  20. A Personalized Approach to Parkinson’s Disease Patients Based on Founder Mutation Analysis

    PubMed Central

    Giladi, Nir; Mirelman, Anat; Thaler, Avner; Orr-Urtreger, Avi

    2016-01-01

    While the phenotype of Parkinson disease (PD) is heterogeneous, treatment approaches are mostly uniform. Personalized medicine aims to treat diseases with targeted therapies based on cumulative variables, including genotype. We believe that sufficient evidence has accumulated to warrant the initiation of personalized medicine in PD based on subjects genotype and provide examples for our reasoning from observations of GBA and LRRK2 mutations carriers. While PD patients who carry the G2019S mutation in the LRRK2 gene seem to develop relatively mild disease with more frequent postural instability gait disturbance phenotype, carriers of mutations in the GBA gene tend to have an early onset, rapidly deteriorating disease, with more pronounced cognitive and autonomic impairments. These characteristics have significant implications for treatment and outcome and should be addressed from an early stage in the attempt to improve the patient’s quality of life. PMID:27242656

  1. Genetic structure of the Newfoundland and Labrador population: founder effects modulate variability.

    PubMed

    Zhai, Guangju; Zhou, Jiayi; Woods, Michael O; Green, Jane S; Parfrey, Patrick; Rahman, Proton; Green, Roger C

    2016-07-01

    The population of the province of Newfoundland and Labrador (NL) has been a resource for genetic studies because of its historical isolation and increased prevalence of several monogenic disorders. Controversy remains regarding the genetic substructure and the extent of genetic homogeneity, which have implications for disease gene mapping. Population substructure has been reported from other isolated populations such as Iceland, Finland and Sardinia. We undertook this study to further our understanding of the genetic architecture of the NL population. We enrolled 494 individuals randomly selected from NL. Genome-wide SNP data were analyzed together with that from 14 other populations including HapMap3, Ireland, Britain and Native American samples from the Human Genome Diversity Project. Using multidimensional scaling and admixture analysis, we observed that the genetic structure of the NL population resembles that of the British population but can be divided into three clusters that correspond to religious/ethnic origins: Protestant English, Roman Catholic Irish and North American aboriginals. We observed reduced heterozygosity and an increased inbreeding coefficient (mean=0.005), which corresponds to that expected in the offspring of third-cousin marriages. We also found that the NL population has a significantly higher number of runs of homozygosity (ROH) and longer lengths of ROH segments. These results are consistent with our understanding of the population history and indicate that the NL population may be ideal for identifying recessive variants for complex diseases that affect populations of European origin. PMID:26669659

  2. A resolution celebrating the life and achievements of Millard Fuller, the founder of Habitat for Humanity.

    THOMAS, 111th Congress

    Sen. Shelby, Richard C. [R-AL

    2009-06-11

    06/11/2009 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (consideration: CR S6570; text as passed Senate: CR S6570; text of measure as introduced: CR S6568) (All Actions) Tracker: This bill has the status Passed SenateHere are the steps for Status of Legislation:

  3. Integrated analyses of gene expression and genetic association studies in a founder population

    PubMed Central

    Cusanovich, Darren A.; Caliskan, Minal; Billstrand, Christine; Michelini, Katelyn; Chavarria, Claudia; De Leon, Sherryl; Mitrano, Amy; Lewellyn, Noah; Elias, Jack A.; Chupp, Geoffrey L.; Lang, Roberto M.; Shah, Sanjiv J.; Decara, Jeanne M.; Gilad, Yoav; Ober, Carole

    2016-01-01

    Genome-wide association studies (GWASs) have become a standard tool for dissecting genetic contributions to disease risk. However, these studies typically require extraordinarily large sample sizes to be adequately powered. Strategies that incorporate functional information alongside genetic associations have proved successful in increasing GWAS power. Following this paradigm, we present the results of 20 different genetic association studies for quantitative traits related to complex diseases, conducted in the Hutterites of South Dakota. To boost the power of these association studies, we collected RNA-sequencing data from lymphoblastoid cell lines for 431 Hutterite individuals. We then used Sherlock, a tool that integrates GWAS and expression quantitative trait locus (eQTL) data, to identify weak GWAS signals that are also supported by eQTL data. Using this approach, we found novel associations with quantitative phenotypes related to cardiovascular disease, including carotid intima-media thickness, left atrial volume index, monocyte count and serum YKL-40 levels. PMID:26931462

  4. Monod as the founder of a new discipline: local and international contexts.

    PubMed

    de Chadarevian, Soraya

    2015-06-01

    Monod gained stature as an experimentalist and theorist as well as a discipline builder. The essay reviews the intimate connection of the intellectual and institutional projects in his career. A brief comparison with the development of the new science of molecular biology across the English Channel highlights the commonalities and specificities of the disciplinary projects in France and Britain and the role that individuals like Monod played in their formation. The article argues that there was not a single path that led to the rise of molecular biology. Rather individual initiatives and historical contingencies very much shaped local outcomes.

  5. [Michael Lazarevich Gershanovich--one of the founders of cancer chemotherapy in Russia].

    PubMed

    Semiglazova, T Iu; Filatova, L V; Stukov, A N

    2014-01-01

    Michael Lazarevich Gershanovich was born 90 years ago. He has made a significant contribution to foundation and development of chemotherapy for malignant tumors. Doctor of Medical Sciences, Professor, Laureate of the State Prize of the Russian Federation, Honored Scientist of the Russian Federation, Academician of the Russian Academy of Natural Sciences, a member of the Editorial Board of the Journal "Problems in Oncology" ("Voprosy Onkologii), member of the World Club of Petersburgians, a retired lieutenant-colonel Michael Lazarevich, until his last day (16.12.2013), was the head of the Department of Medical Oncology of the N.N.Petrov Research Institute of Oncology, St. Petersburg. PMID:25552077

  6. Whole-genome sequencing of individuals from a founder population identifies candidate genes for asthma.

    PubMed

    Campbell, Catarina D; Mohajeri, Kiana; Malig, Maika; Hormozdiari, Fereydoun; Nelson, Benjamin; Du, Gaixin; Patterson, Kristen M; Eng, Celeste; Torgerson, Dara G; Hu, Donglei; Herman, Catherine; Chong, Jessica X; Ko, Arthur; O'Roak, Brian J; Krumm, Niklas; Vives, Laura; Lee, Choli; Roth, Lindsey A; Rodriguez-Cintron, William; Rodriguez-Santana, Jose; Brigino-Buenaventura, Emerita; Davis, Adam; Meade, Kelley; LeNoir, Michael A; Thyne, Shannon; Jackson, Daniel J; Gern, James E; Lemanske, Robert F; Shendure, Jay; Abney, Mark; Burchard, Esteban G; Ober, Carole; Eichler, Evan E

    2014-01-01

    Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow-up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS. PMID:25116239

  7. Disclosure of genetic research results to members of a founder population.

    PubMed

    Anderson, Rebecca L; Murray, Kathleen; Chong, Jessica X; Ouwenga, Rebecca; Antillon, Marina; Chen, Peixian; Diaz de Leon, Lorena; Swoboda, Kathryn J; Lester, Lucille A; Das, Soma; Ober, Carole; Waggoner, Darrel J

    2014-12-01

    There is currently extensive discussion and debate in the literature on how, when, and to whom genetic research results should be returned (see Genetics in Medicine, April 2012 issue). Here, we describe our experience in disclosing genetic information on Mendelian disorders discovered during the course of our research in the Hutterites. We first assessed attitudes toward the disclosure of carrier results, which revealed that many individuals wanted carrier information and that many intended to use the information in family planning. Based on this information, we developed a pilot study to test and disclose cystic fibrosis (CF) carrier status. Next, a larger scale project was developed in order to disclose genetic research results for 14 diseases to those interested in receiving the information. We developed brochures, offered a live interactive educational program, conducted a consent process, and disclosed results in letters mailed to the consented individuals. Overall, ~80% of individuals who participated in the educational program signed consent forms for the release of their results for 14 diseases. We describe our experience with returning individual genetic research results to participants in a population-based research study. PMID:24777552

  8. Diluting the founder effect: cryptic invasions expand a marine invader's range

    PubMed Central

    Roman, Joe

    2006-01-01

    Most invasion histories include an estimated arrival time, followed by range expansion. Yet, such linear progression may not tell the entire story. The European green crab (Carcinus maenas) was first recorded in the US in 1817, followed by an episodic expansion of range to the north. Its population has recently exploded in the Canadian Maritimes. Although it has been suggested that this northern expansion is the result of warming sea temperatures or cold-water adaptation, Canadian populations have higher genetic diversity than southern populations, indicating that multiple introductions have occurred in the Maritimes since the 1980s. These new genetic lineages, probably from the northern end of the green crab's native range in Europe, persist in areas that were once thought to be too cold for the original southern invasion front. It is well established that ballast water can contain a wide array of nonindigenous species. Ballast discharge can also deliver genetic variation on a level comparable to that of native populations. Such gene flow not only increases the likelihood of persistence of invasive species, but it can also rapidly expand the range of long-established nonindigenous species. PMID:16959635

  9. [The cognitive process of Robert Koch in becoming the founder of tuberculosis control].

    PubMed

    Steinbrück, P

    1983-01-01

    The development of Robert Koch to a scientist with enormous effects to the picture of modern medicine and society is interpreted from the point of view of today. Koch has critically acquired the great scientific progress of his time by reason of his excellent gifts; he has confirmed them and has extended them fundamentally by his discoveries. Koch possessed the prerequisites for it due to his systematic, persevering and comprehensive way of working and his assiduity making him one of the originators of bacteriology, the creator of the control of infectious diseases and above all of tuberculosis. His commitment to helping men and community wherever necessary with all his possibilities, has made him a benefactor to humanity.

  10. Whole-genome sequencing of individuals from a founder population identifies candidate genes for asthma.

    PubMed

    Campbell, Catarina D; Mohajeri, Kiana; Malig, Maika; Hormozdiari, Fereydoun; Nelson, Benjamin; Du, Gaixin; Patterson, Kristen M; Eng, Celeste; Torgerson, Dara G; Hu, Donglei; Herman, Catherine; Chong, Jessica X; Ko, Arthur; O'Roak, Brian J; Krumm, Niklas; Vives, Laura; Lee, Choli; Roth, Lindsey A; Rodriguez-Cintron, William; Rodriguez-Santana, Jose; Brigino-Buenaventura, Emerita; Davis, Adam; Meade, Kelley; LeNoir, Michael A; Thyne, Shannon; Jackson, Daniel J; Gern, James E; Lemanske, Robert F; Shendure, Jay; Abney, Mark; Burchard, Esteban G; Ober, Carole; Eichler, Evan E

    2014-01-01

    Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow-up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS.

  11. Rapid increase in southern elephant seal genetic diversity after a founder event.

    PubMed

    de Bruyn, Mark; Pinsky, Malin L; Hall, Brenda; Koch, Paul; Baroni, Carlo; Hoelzel, A Rus

    2014-03-22

    Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population.

  12. [Felix Vicq d'Azyr, founder of the Academy of Medicine (1748-1794)].

    PubMed

    Sournia, J C

    1994-10-01

    Vicq d'Azyr (1748-1794) was the son of a norman physician. He was graduated at the Paris university and obtained quickly a brilliant renown and career. During his whole life he continued studies on human and animal anatomy. Member of Académie des sciences and Académie française, he was the queen's physician, superintendent for epidemies, and above all general secretary of the Société royale de médecine. In that position he kept a regular correspondence with a great number of physicians and surgeons in the Kingdom. They gave the Société informations about epidemies and epizooties in relation with the climate, about economic resources of the population, the quality of food supplies, the ability of health professionals, etc. The amount of the informations so collected during sixteen years is considerable. Vicq d'Azyr also worked out a plan for setting up the medicine in the country. That plan was based on public physicians in countries, districts and departments, giving an "academic body" an account of their task. His vow was satisfied in 1820 when the Académie royale de médecine was founded.

  13. Diluting the founder effect: cryptic invasions expand a marine invader's range.

    PubMed

    Roman, Joe

    2006-10-01

    Most invasion histories include an estimated arrival time, followed by range expansion. Yet, such linear progression may not tell the entire story. The European green crab (Carcinus maenas) was first recorded in the US in 1817, followed by an episodic expansion of range to the north. Its population has recently exploded in the Canadian Maritimes. Although it has been suggested that this northern expansion is the result of warming sea temperatures or cold-water adaptation, Canadian populations have higher genetic diversity than southern populations, indicating that multiple introductions have occurred in the Maritimes since the 1980s. These new genetic lineages, probably from the northern end of the green crab's native range in Europe, persist in areas that were once thought to be too cold for the original southern invasion front. It is well established that ballast water can contain a wide array of nonindigenous species. Ballast discharge can also deliver genetic variation on a level comparable to that of native populations. Such gene flow not only increases the likelihood of persistence of invasive species, but it can also rapidly expand the range of long-established nonindigenous species. PMID:16959635

  14. Academy of Breastfeeding Medicine Founder's Lecture 2008: Breastfeeding—An Extrauterine Link Between Mother and Child

    PubMed Central

    Walker, W. Allan

    2009-01-01

    Abstract In addition to a near-optimal combination of nutrients for the growing infant, breastmilk contains a wide array of bioactive molecules that are known to protect the infant against infectious disease and modulate the composition of the indigenous intestinal microbiota. A growing number of factors that modulate the infant's immunophysiology have also been identified in breastmilk. We suggest that this early immunomodulation via breastmilk is vital for infant health and may explain the epidemiological data indicating that breastmilk reduces the risk of immunoinflammatory conditions in infancy and also later in life. The body of scientific data regarding the role of transforming growth factor-β in breastmilk in enhancing healthy immune maturation and reducing the risk of disease is reviewed in this article. PMID:19292608

  15. Asian/Pacific American Librarians Association--A History of APALA and Its Founders.

    ERIC Educational Resources Information Center

    Yamashita, Kenneth A.

    2000-01-01

    Describes the societal and professional, as well as the personal, contexts which motivated the creation of the Asian/Pacific American Librarians Association (APALA) and its predecessor, the Asian American Librarians Caucus/Association (AALC/A). Includes profiles of the Asian/Pacific American library leaders who established these organizations and…

  16. [Volodymyr Petrovych Vendt--a founder of sceintific trends in photobiochemistry and biotechnology in Ukraine].

    PubMed

    2006-01-01

    Professor Volodymyr Petrovych Vendt (30.11.1906, Kremenchug, Ukraine-22.11.1997, Kyiv, Ukraine), Doctor of science (biol.), Laureate of the State Prize of Ukraine graduated from the Odessa Physico-Pharmaceutical Institute (1930) in speciality chemist-analyst and was assigned to work at the Ukrainian Institute of Pathology and Labour Hygiene in Kharkiv. He was soon taken on as a scientific worker at the Ukrainian Institute of Experimental Medicine. He defended his thesis for the Candidate's degree and acquired the academic status of the senior scientific worker in 1939, and that of docent (assistant professor) in 1940. In 1938-1941 Volodymyr Petrovych read lectures at the Department of Chemistry of the Academy of Service Corps of the Workers' and Peasants' Red Army. At that time his scientific interests were connected with development of simple express-methods for detecting various substances, including chemical weed- and pest-killers which were used in agriculture. In 1944-1946 V. P. Vendt took part in military operations at the 1st Ukrainian Front, and after the release he was taken on as the senior scientific worker at the Institute of Biochemistry of the Academy of Sciences of the Ukrainian SSR, where he worked during 47 years. In 1961, after defending the thesis for the Doctor's degree Volodymyr Petrovych acquired the academic status of professor. In 1963 V. P. Vendt became a head of the Laboratory and then (1966) - of the Deaprtment of Photobiochemistry and from 1976 to 1983 - the Department of Sterol Biochemistry. He was the first to make the broad-scale investigations of sterol biochemistry, first of all group D vitamins, and came close to finding out the action mechanism of vitamin D3 - cholecalciferol. V. P. Vendt was one of the first to show a possibility of formation of sterene complexes with proteins and to find out the nature of chemical relations between them. That made it possible to develop the methods of obtaining artificial protein-vitamin complexes of high activity on the basis of casein (or other proteins) with preparations of vitamins D2, D3, E, carotene. Vitamin industry of the USSR used the technology, elaborated by V. P. Vendt, for the industrial production of vitamin D3 (videin D3) for poultry farming and medicine. He offered the method of early diagnosis of D-hypovitaminosis in chickens and developed and put into medical practice the methods of early diagnosis of rachitis in children and the degree of the disease risk by the umbilical blood analysis. V. P. Vendt and R. I. Yakhymovych were the first to obtain crystalline vitamin D3 and its complex with cholesterol (videchol) which was successfully used for rachitis prophylaxis and therapy in children. V. P. Vendt is the author of above 200 scientific works, 17 author's certificates and inventions. The scientific school of V. P. Vendt numbers 4 doctors and 16 candidates of science and above 60 research workers. The selfless work of the scientist was marked by state awards--by six medals and the State Prize of Ukraine in the field of science and technology "For investigations in vitamin D chemistry and biochemistry, creation of industrial technology of its production and introduction into medicine and agriculture" (jointly with R. I. Yakhymovych). PMID:17236620

  17. Recycling of lower continental crust through foundering of cumulates from contaminated mafic intrusions

    NASA Technical Reports Server (NTRS)

    Arndt, Nicholas T.; Goldstein, Steven L.

    1988-01-01

    A mechanism is presented for recycling of lower continental material back into the mantle. Picritic magmas, possible parental to volumious continental volcanics such as the Karoo and Deccan, became trapped at the Moho, where they interacted with and become contaminated by lower crustal materials. Upon crystallization, the magmas differentiated into lower ultramafic cumulate zones and upper gabbroic-anorthositic zones. The ultramafic cumulates are denser than underlying mantle and sink, carrying lower crustal components as trapped liquid, as xenoliths or rafts, and as constituents of cumulate minerals. This model provides a potentially significant crust-mantle differentiation mechanism, and may also represent a contributing factor in crustal recycling, possibly important in producing some OIB reservoirs.

  18. Founders, Finding, Being Found: Women's Wisdom in Teaching and Learning in Theology and Religion

    ERIC Educational Resources Information Center

    Hess, Lisa M.; Brosmer, Mary Pierce; Moore, Mary Elizabeth Mullino

    2015-01-01

    This is an edited transcript of a conversation between two founding women on the delights and demands of teaching and learning within and beyond traditional institutional life, facilitated by Lisa M. Hess of the journal's Editorial Board. The conscious feminine practices of a women's writing school, Women Writing for (a) Change (Cincinnati, Ohio),…

  19. The migrations of Drosophila muscle founders and primordial germ cells are interdependent.

    PubMed

    Stepanik, Vincent; Dunipace, Leslie; Bae, Young-Kyung; Macabenta, Frank; Sun, Jingjing; Trisnadi, Nathanie; Stathopoulos, Angelike

    2016-09-01

    Caudal visceral mesoderm (CVM) cells migrate from posterior to anterior of the Drosophila embryo as two bilateral streams of cells to support the specification of longitudinal muscles along the midgut. To accomplish this long-distance migration, CVM cells receive input from their environment, but little is known about how this collective cell migration is regulated. In a screen we found that wunen mutants exhibit CVM cell migration defects. Wunens are lipid phosphate phosphatases known to regulate the directional migration of primordial germ cells (PGCs). PGC and CVM cell types interact while PGCs are en route to the somatic gonadal mesoderm, and previous studies have shown that CVM impacts PGC migration. In turn, we found here that CVM cells exhibit an affinity for PGCs, localizing to the position of PGCs whether mislocalized or trapped in the endoderm. In the absence of PGCs, CVM cells exhibit subtle changes, including more cohesive movement of the migrating collective, and an increased number of longitudinal muscles is found at anterior sections of the larval midgut. These data demonstrate that PGC and CVM cell migrations are interdependent and suggest that distinct migrating cell types can coordinately influence each other to promote effective cell migration during development. PMID:27578182

  20. Family Business Succession: Founders from Disadvantaged Communities in South Africa--An Exploratory Study

    ERIC Educational Resources Information Center

    Isaacs, Eslyn B. H.; Friedrich, Christian

    2011-01-01

    It is estimated that 50-70% of all South African businesses are family-owned and that these businesses form the backbone of the South African economy, their qualities providing stability and resilience in the changing society of the nation. Succession is one of the biggest challenges for family business owners. Research shows that only 33% of all…

  1. Whole-Genome Sequencing of Individuals from a Founder Population Identifies Candidate Genes for Asthma

    PubMed Central

    Campbell, Catarina D.; Mohajeri, Kiana; Malig, Maika; Hormozdiari, Fereydoun; Nelson, Benjamin; Du, Gaixin; Patterson, Kristen M.; Eng, Celeste; Torgerson, Dara G.; Hu, Donglei; Herman, Catherine; Chong, Jessica X.; Ko, Arthur; O'Roak, Brian J.; Krumm, Niklas; Vives, Laura; Lee, Choli; Roth, Lindsey A.; Rodriguez-Cintron, William; Rodriguez-Santana, Jose; Brigino-Buenaventura, Emerita; Davis, Adam; Meade, Kelley; LeNoir, Michael A.; Thyne, Shannon; Jackson, Daniel J.; Gern, James E.; Lemanske, Robert F.; Shendure, Jay; Abney, Mark; Burchard, Esteban G.; Ober, Carole; Eichler, Evan E.

    2014-01-01

    Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow-up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS. PMID:25116239

  2. John Jones, M.D.: pioneer, patriot, and founder of American surgery.

    PubMed

    Griesemer, Adam D; Widmann, Warren D; Forde, Kenneth A; Hardy, Mark A

    2010-04-01

    John Jones was a pioneer of American Surgery. Born in Long Island, New York in 1729, he received his medical degree in France from the University of Rheims. He returned to the colonies and helped to establish the medical school that would later become Columbia University's College of Physicians and Surgeons where he was appointed the first Professor of Surgery in the New World. He used his position to assert that surgeons trained in America should be familiar with all facets of medicine and not be mere technicians. Before the outbreak of the American Revolution, he wrote a surgical field manual, which was the first medical text published in America. A believer in the principles of the American Revolution, he would go on to count Benjamin Franklin and George Washington as his patients. Despite achieving many firsts in American medicine, his influence on surgical training is his most enduring legacy.

  3. [Doctor Levi B. Salmans, founder of The Good Samaritan sanitarium in Guanajuato].

    PubMed

    Olivier-Toledo, Carlos; Viesca-Treviño, Carlos

    2016-01-01

    In this research we focus on the medical evangelist Levi B. Salmans, and The Good Samaritan sanitarium. Doctor Salmans lived in Mexico for about 50 years (1885-1935). During the first part of his stay, he was devoted to found churches and Methodist schools. However, from 1891 he took a turn in his career by founding dispensaries in different towns of Guanajuato to create, in 1899, the private charity association for the sick and infirm The Good Samaritan. His intense, intellectual, and practical work led him to create health journals, to train nurses, and to promote physiotherapies in accordance with the science advances of that time. By itself, this research shows that the history of medicine in Mexico still has long way to go and that Protestant communities, in favor of modernity and scientific knowledge, took a big part in shaping the history of this discipline in Mexico. PMID:27100985

  4. Moving Forward from the Past: Early Writings and Current Reflections of Middle School Founders.

    ERIC Educational Resources Information Center

    David, Robert, Ed.

    Twenty-three articles by five educators who wrote in the 1960's and 1970's about the then new concept of the middle school are gathered, along with current essays reflecting on the insight these papers provide for current middle-school concerns. In the first section, C. Kenneth McEwin reflects on the current impact of these writings of William M.…

  5. The skaergaard layered series. Part IV. reaction-transport simulations of foundered blocks.

    SciTech Connect

    Sonnenthal, Eric L.; McBirney, Alexander R.

    1996-01-02

    During the middle stages of crystallization of the Skaergaard Layered Series large numbers of blocks became detached from the Upper Border Series and settled into the mush of crystals on the floor. It has been recognized for some time that these blocks now have compositions and textures that differ markedly from those of the units from which they came. They tend to be more plagioclase rich and seem to have lost mafic components to the surrounding gabbro. Numerical simulations coupling crystallization, melting, and heat and mass transfer for a multicomponent system show how the blocks reacted with the mush in which they were emplaced. Enhanced cooling and crystallization of a compositionally stratified mush adjacent to the blocks resulted in patterns of melt compositions similar to those of layering around the blocks. Volume changes during crystallization and melting induced convection of the interstitial melt leading to changes in the bulk compositions of the blocks and the surrounding mush. Inhomogeneities such as inclusions are likely to facilitate the onset of compositional convection in a chemically stratified solidification zone.

  6. Developing exchange/recombinase founder lines to introduce huanglongbing (HLB) resistance genes into citrus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have designed an innovative system to to deploy a novel pair of recombinase enzymes, namely Bxb1 and CinH, for performing precise genetic engineering of citrus (Thomson et al. 2012). They control the integration and the excision of sequences based on the presence and orientation of specific recog...

  7. Consensus on diagnosis and management of JME: From founder's observations to current trends.

    PubMed

    Kasteleijn-Nolst Trenité, Dorothée G A; Schmitz, Bettina; Janz, Dieter; Delgado-Escueta, Antonio V; Thomas, Pierre; Hirsch, Edouard; Lerche, Holger; Camfield, Carol; Baykan, Betul; Feucht, Martha; Martínez-Juárez, Iris E; Duron, Reyna M; Medina, Marco T; Rubboli, Guido; Jerney, Judith; Hermann, Bruce; Yacubian, Elza; Koutroumanidis, Michael; Stephani, Ulrich; Salas-Puig, Javier; Reed, Ronald C; Woermann, Friedrich; Wandschneider, Britta; Bureau, Michelle; Gambardella, Antonio; Koepp, Matthias J; Gelisse, Philippe; Gurses, Cardan; Crespel, Arielle; Nguyen-Michel, Vi Huong; Ferlazzo, Edoardo; Grisar, Thierry; Helbig, Ingo; Koeleman, Bobby P C; Striano, Pasquale; Trimble, Michael; Buono, Russel; Cossette, Patrick; Represa, Alfonso; Dravet, Charlotte; Serafini, Anna; Berglund, Ivanka Savic-; Sisodiya, Sanjay M; Yamakawa, Kazuhiro; Genton, Pierre

    2013-07-01

    An international workshop on juvenile myoclonic epilepsy (JME) was conducted in Avignon, France in May 2011. During that workshop, a group of 45 experts on JME, together with one of the founding fathers of the syndrome of JME ("Janz syndrome"), Prof. Dr. Dieter Janz from Berlin, reached a consensus on diagnostic criteria and management of JME. The international experts on JME proposed two sets of criteria, which will be helpful for both clinical and scientific purposes. Class I criteria encompass myoclonic jerks without loss of consciousness exclusively occurring on or after awakening and associated with typical generalized epileptiform EEG abnormalities, with an age of onset between 10 and 25. Class II criteria allow the inclusion of myoclonic jerks predominantly occurring after awakening, generalized epileptiform EEG abnormalities with or without concomitant myoclonic jerks, and a greater time window for age at onset (6-25years). For both sets of criteria, patients should have a clear history of myoclonic jerks predominantly occurring after awakening and an EEG with generalized epileptiform discharges supporting a diagnosis of idiopathic generalized epilepsy. Patients with JME require special management because their epilepsy starts in the vulnerable period of adolescence and, accordingly, they have lifestyle issues that typically increase the likelihood of seizures (sleep deprivation, exposure to stroboscopic flashes in discos, alcohol intake, etc.) with poor adherence to antiepileptic drugs (AEDs). Results of an inventory of the different clinical management strategies are given. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?

  8. By All Means, Study the Founders: Notes from the Democratic Left

    ERIC Educational Resources Information Center

    Street, Paul

    2003-01-01

    A thesis concocted by right-wing ideological watchdogs and advanced with elevated urgency in the wake September 11, 2001, claims that America's college and university students are hostage to a leftist, "moral-relativist" and multiculturalist professoriat. To restore right-thinking to college campuses, the argument continues, academic authority…

  9. Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity

    SciTech Connect

    Chiurazzi, P.; Genuardi, M.; Kozak, L.; Neri, G.

    1996-07-12

    A total of 137 fragile X and 235 control chromosomes from various regions of Italy were haplotyped by analyzing two neighbouring marker microsatellites, FRAXAC1 and DXS548. The number of CGG repeats at the 5{prime} end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some {open_quotes}major{close_quotes} haplotypes and fragile X was observed, while other {open_quotes}minor{close_quotes} haplotypes may have originated by subsequent mutation at the marker microsatellite loci and/or recombination between them. Recent evidence suggests that the initial mechanism leading to CGG instability might consist of rare (10{sup -6/-7}) CGG repeat slippage events and/or loss of a stabilizing AGG via A-to-C transversion. Also, the apparently high variety of fragile X chromosomes may be partly due to the relatively high mutation rate (10{sup -4/-5}) of the microsatellite markers used in haplotyping. Our fragile X sample also showed a higher than expected heterozygosity when compared to the control sample and we suggest that this might be explained by the chance occurrence of the few founding events on different chromosomes, irrespective of their actual frequency in the population. Alternatively, a local mechanism could enhance the microsatellite mutation rate only on fragile X chromosomes, or fragile X mutations might occur more frequently on certain background haplotypes. 59 refs., 4 figs.

  10. [Volodymyr Oleksandrovych Bielitser--a gifted scientist and outstanding biochemist, a founder of the scientific school].

    PubMed

    2006-01-01

    Professor V. O. Belitser, Doctor of Science (biology), (30.09.1906, Ryazan, RF-04.03.1988 Kyiv, Ukraine), Member of the National Academy of Sciences of Ukraine, graduated from the physico-mathematical faculty of the Moscow University in speciality "physico-chemical biology". In 1934-1943 he worked at the All-Union Institute of Experimental Medicine (Moscow) where he was engaged in research of the relation between the respiratory system and glycolytic reactions in the animal tissues. V. O. Belitser established the effect of creatin on the muscular respiration on the role of creative phosphate in this process. He was the first to demonstrate that the anaerobic phosphorylation is bound to respiration. He investigated stechiometric relations between the joint phosphate binding and oxygen absorption and estimated thermodynamic importance of this process, he showed that the energy of electron transfer from the substrate to oxygen is a source of formation of three ATP molecules per one atom of absorbed oxygen. From 1944 to 1988 V. O. Belitser worked at the Institute of Biochemistry of the Academy of Sciences of the Ukr.SSR (Kyiv), where he headed the Laboratory of Enzymes (then proteins), and from 1966 he headed the Department of Protein Structure and Function; for a certain period (1969-1972) he headed the Institute as its director. Investigations of properties of native and denaturated proteins jointly with K. I. Kotkova led to the creation of blood substitute from blood serum proteins of cattle--BK-8. The school of V. O. Belitser is known by studying the molecular mechanism of one of the basic reactions of blood coagulation--fibrinogen transformation to fibrin, by finding out the organization and function of fibrinogen and fibrin. It was proved experimentally that the specific polymerization centres significance for the fibrin lattice formation are of essential significance for the fibrin lattice formation, that fibrinogen to fibrin transformation occurs in two stages--enzymatic and polymerizational ones. V. O. Belitser proposed the mechanism of fibrinogen transformation to fibrin, as soon as he had substantiated the kinetic theory of this reaction; domain structure of fibrinogen has been investigated. Such diagnostic tests as the methods of definition of the products of fibrinogen and fibrin splitting in urine (for differential diagnosis of cardiovascular diseases) were developed and put into medical practice under his guidance. V. O. Belitser and members of his school have published above 300 scientific works, prepared 5 doctors and 25 candidates of science. The selfless work of the scientists was honoured with high state awards--the Orders of Lenin, the Order of the Labour Red Banner, the Order of Oktober Revolution, that of Friendship of Peoples and with numerous medals.

  11. [T. I. Eroshevskii--founder of the Sarmarsk school of ophthalmology].

    PubMed

    Kotel'nikov, G P; Malov, V M

    2003-01-01

    June 26 is the 100 anniversary of Professor T.I. Yeroshevsky--the Hero of socialist Work, the winner of the USSR State Premium, the correspondent of the USSR Academy of Medical Sciences, the Honoured Scientist of the RSFSR, the Honoured Citizen of Kuibyshev (nowdays--Samara) and Gurkovo of the Bulgarian National Republic. His talent sa a innovator in science, a brilliant teacher, a talented clinician and one of the best organizers was shown in the full during the Samara period of his life. The All-Russia conference of ophthalmologists, two Volga region conferences on glaucoma were held in Kuibyshev. T.I. Yeroshevsky took part in the work of international ophthalmologists congresses in Leipzig and Canada, Kabul and Prague, Cairo and Bagdad, Mexico City and Sofia. All this contributed to the popularity and authority of T.I. Yeroshevsky and the unique union of the ophthalmic hospital with a faculty and problem laboratory. It was the first specialised ophthalmic complex in Russian Federation. Being a remarkable teacher, He trained more than a thousand students--the future doctors. More than 70 doctoral and candidate thesis were carried out and defended under his guidance. T.I. Yerosevsky's scientific interests were very diverse. He started his way in science from the research of transplantation of cornea and he devoted to it his doctoral thesis. The study of primary glaucoma was very significant in his research work. His clinic was one of the first in this country to introduce the photocoagulation of retina. At the beginning of the 1980s it introduced the laser surgery and therapy of various eye diseases. Kuibyshev clinic was also one of the first to master cataract cryoextraction and soon it reached the best results in the world in this direction. The regional clinic ophthalmic hospital, the faculty and problem laboratory are scientific centre of this country, it can be proved by 15 digests of scientific works issued under T.I. Yeroshevsky's edition the republic congress and all-Union ophthalmologist conferences held since 1952. This remarkable tradition is kept nowadays.

  12. Founder of systems chemistry and foundational theoretical biologist: Tibor Gánti (1933-2009).

    PubMed

    Szathmáry, Eörs

    2015-09-21

    With his chemoton theory theoretical biologist and chemical engineer Tibor Gánti was one of the most outstanding intellects behind systems chemistry and the at the foundations of theoretical biology. A brief review of his oeuvre is presented. This essay introduces a special issue dedicated to his memory.

  13. A biography of William Tuke (1732-1822): Founder of the modern mental asylum.

    PubMed

    Kibria, Ayisha A; Metcalfe, Neil H

    2016-08-01

    William Tuke was a 19th-century reformist and philanthropist notable for his work in mental health. He was known for his strict self-discipline and judicious manner. He was also a firm believer in the Quaker faith and actively supported the group and employed many of their principles in his work, especially in his chef d'oeuvre, The Retreat, established in 1792, a mental asylum in York. Possibly catalysed by the very public mismanagement of King George III's 'madness', he pioneered the use of moral treatment, a new humane method of treating mental illness. This focussed on allowing patients to live in a community, partake in daily activities and not be subjected to the brutality of the commonplace asylum, all of which were very rare in the treatment of lunatics at that time. Described as 'The Period of Humane Reform', his work coincided with the emergence of similar approaches in France, most famously by Philippe Pinel (1745-1826) and his pupil Jean Esquirol (1772-1840) in Paris. Tuke eventually went on to aid in the reform of the law with regards to asylums. PMID:24944052

  14. Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population

    PubMed Central

    Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.

    2013-01-01

    Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701

  15. Rapid increase in southern elephant seal genetic diversity after a founder event.

    PubMed

    de Bruyn, Mark; Pinsky, Malin L; Hall, Brenda; Koch, Paul; Baroni, Carlo; Hoelzel, A Rus

    2014-03-22

    Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population. PMID:24478305

  16. [Doctor Levi B. Salmans, founder of The Good Samaritan sanitarium in Guanajuato].

    PubMed

    Olivier-Toledo, Carlos; Viesca-Treviño, Carlos

    2016-01-01

    In this research we focus on the medical evangelist Levi B. Salmans, and The Good Samaritan sanitarium. Doctor Salmans lived in Mexico for about 50 years (1885-1935). During the first part of his stay, he was devoted to found churches and Methodist schools. However, from 1891 he took a turn in his career by founding dispensaries in different towns of Guanajuato to create, in 1899, the private charity association for the sick and infirm The Good Samaritan. His intense, intellectual, and practical work led him to create health journals, to train nurses, and to promote physiotherapies in accordance with the science advances of that time. By itself, this research shows that the history of medicine in Mexico still has long way to go and that Protestant communities, in favor of modernity and scientific knowledge, took a big part in shaping the history of this discipline in Mexico.

  17. We Specialize in the Wholly Impossible: African-American Women School Founders and Their Mission.

    ERIC Educational Resources Information Center

    McCluskey, Audrey Thomas

    Charlotte Hawkins Brown, Mary McLeod Bethune, and Nannie Helen Burroughs were women with a mission. It was a mission that combined educational, social, and economic goals. Although different in their tactics and in their educational programs, these women, who founded schools in the late 19th and early 20th centuries, were united in their belief…

  18. U.S. EPA Environmental Technology Verification Program, the Founder of the ETV Concept

    EPA Science Inventory

    The U.S. EPA Environmental Technology Verification (ETV) Program develops test protocols and verifies the performance of innovative technologies that have the potential to improve protection of human health and the environment. The program was created in 1995 to help accelerate t...

  19. Influences on the Founder of the Johns Hopkins University and the Johns Hopkins Medical School.

    ERIC Educational Resources Information Center

    Parker, Franklin

    1994-01-01

    Explains how George Peabody, self-made millionaire and educational philanthropist, was one of three powerful men who influenced Johns Hopkins in founding Johns Hopkins University (the other two being Dr. Joseph Parrish and Dr. Patrick Macaulay). The article looks at how Hopkins, like Peabody, used his wealth for philanthropic purposes. (SM)

  20. Founders of "Liberal Education": The Case for Roman Orators against Socratic Philosophers.

    ERIC Educational Resources Information Center

    Kimball, Bruce A.

    1983-01-01

    The author argues that the graduate of the "artes liberales" (liberal arts) is the Roman orator, trained to defend persuasively the right and just, and not the person devoted to the Socratically-based introspective search for truth, as many contemporary academicians would maintain. (JMK)

  1. A Second-Generation Genomewide Screen for Asthma-Susceptibility Alleles in a Founder Population

    PubMed Central

    Ober, Carole; Tsalenko, Anya; Parry, Rodney; Cox, Nancy J.

    2000-01-01

    A genomewide screen for asthma- and atopy-susceptibility loci was conducted, using 563 markers, in 693 Hutterites who are members of a single 15-generation pedigree, nearly doubling the sample size from the authors' earlier studies. The resulting increase in power led to the identification of 23 loci in 18 chromosomal regions showing evidence for linkage that is, in general, 10-fold more significant (P<.001 vs. P<.01) than the linkages reported previously in this population. Moreover, linkages to loci in 11 chromosomal regions were identified for the first time in the Hutterites in this report, including five regions (5p, 5q, 8p, 14q, and 16q) showing evidence both of linkage, by the likelihood ratio (LR) χ2, and of disequilibrium, by the transmission/disequilibrium test. A region on chromosome 19 continues to show evidence for linkage, by both tests, in this study. Studies of 17 candidate genes provide evidence for association with variation in the IL4RA gene (16p12), the HLA class II genes (6p21), and the interferon-α gene cluster (9p22), but the lack of evidence for linkage in these regions by the LR χ2 test suggests that these are minor susceptibility loci. A polymorphism in the CD14 gene is in linkage disequilibrium with an as yet unidentified susceptibility allele in the 5q cytokine cluster, a region showing evidence for linkage among the Hutterites. Finally, 10 of the regions showing evidence for linkage in the Hutterites have shown evidence of linkage to related phenotypes in other genome screens, suggesting that these regions may contain common alleles that have relatively large effects on asthma and atopy phenotypes in diverse populations. PMID:11022011

  2. The founder and head of the Chair of Theoretical Physics of the Yerevan State University

    NASA Astrophysics Data System (ADS)

    Grigoryan, L. Sh

    2014-03-01

    The paper is dedicated to the Centenary of an Academician of NAS RA, Professor G S Sahakyan's birth, the Man that founded and headed the Chair of Theoretical Physics (CTP) of the Yerevan State University for almost half a century. The reference to school days of G S Sahakyan is made, information about his 7 years long service in the forces in the fields, about the establishment and administration by him of the Chair of Theoretical Physics in the Yerevan State University, about his collaboration with academician V A Ambartsumian, about the research associates of the G S Sahakyan's Chair, the students of CTP and the advancement of theoretical physics in Armenia is given. The personality characteristics of G S Sahakyan as a principal investigator and leader of CTP are analyzed.

  3. Baron Dominique-Jean Larrey (1766-1842): founder of military surgery and trauma care.

    PubMed

    Karamanou, M; Rosenberg, T; Liakakos, T; Androutsos, G

    2011-01-01

    Dominique-Jean Larrey was a distinguished surgeon in chief of Napoleon's army and a faithful servant of the Empire. His surgical skills and inventions, his absolute attachment and devotion to his profession, his humanitarian spirit and courage entitled him as one of history's greatest military surgeons. PMID:21520773

  4. Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis.

    PubMed

    Prochazka, Jan; Prochazkova, Michaela; Du, Wen; Spoutil, Frantisek; Tureckova, Jolana; Hoch, Renee; Shimogori, Tomomi; Sedlacek, Radislav; Rubenstein, John L; Wittmann, Torsten; Klein, Ophir D

    2015-12-21

    The proper positioning of organs during development is essential, yet little is known about the regulation of this process in mammals. Using murine tooth development as a model, we have found that cell migration plays a central role in positioning of the organ primordium. By combining lineage tracing, genetic cell ablation, and confocal live imaging, we identified a migratory population of Fgf8-expressing epithelial cells in the embryonic mandible. These Fgf8-expressing progenitors furnish the epithelial cells required for tooth development, and the progenitor population migrates toward a Shh-expressing region in the mandible, where the tooth placode will initiate. Inhibition of Fgf and Shh signaling disrupted the oriented migration of cells, leading to a failure of tooth development. These results demonstrate the importance of intraepithelial cell migration in proper positioning of an initiating organ.

  5. Shoma Morita, founder of Morita therapy, and haiku poet Shiki: origin of Morita therapy.

    PubMed

    Moriyama, N

    1991-12-01

    A hypothesis that Shiki's struggle for life probably influenced the creation of Morita therapy is presented. Although Morita had no personal acquaintance with Shiki, they did have three common friends in Terada, Wakao and Katori. Considering this, as well as the renown of Shiki's works, Morita likely knew much of Shiki and may have been deeply impressed by his approach to life. Several essential concepts of Morita therapy such as absolute bed-rest, anguish and deliverance, "Arugamama," "Jijitsu Yuishin," desire to live, and the importance of keeping a diary can be found in Shiki's lifestyle and in his literary theory. PMID:1813675

  6. Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations.

    PubMed Central

    Telatar, M; Teraoka, S; Wang, Z; Chun, H H; Liang, T; Castellvi-Bel, S; Udar, N; Borresen-Dale, A L; Chessa, L; Bernatowska-Matuszkiewicz, E; Porras, O; Watanabe, M; Junker, A; Concannon, P; Gatti, R A

    1998-01-01

    To facilitate the evaluation of ATM heterozygotes for susceptibility to other diseases, such as breast cancer, we have attempted to define the most common mutations and their frequencies in ataxia-telangiectasia (A-T) homozygotes from 10 ethnic populations. Both genomic mutations and their effects on cDNA were characterized. Protein-truncation testing of the entire ATM cDNA detected 92 (66%) truncating mutations in 140 mutant alleles screened. The haplotyping of patients with identical mutations indicates that almost all of these represent common ancestry and that very few spontaneously recurring ATM mutations exist. Assays requiring minimal amounts of genomic DNA were designed to allow rapid screening for common ethnic mutations. These rapid assays detected mutations in 76% of Costa Rican patients (3), 50% of Norwegian patients (1), 25% of Polish patients (4), and 14% of Italian patients (1), as well as in patients of Amish/Mennonite and Irish English backgrounds. Additional mutations were observed in Japanese, Utah Mormon, and African American patients. These assays should facilitate screening for A-T heterozygotes in the populations studied. PMID:9443866

  7. Identification, Molecular Cloning, and Analysis of Full-Length Hepatitis C Virus Transmitted/Founder Genotypes 1, 3, and 4

    PubMed Central

    Stoddard, Mark B.; Li, Hui; Wang, Shuyi; Saeed, Mohsan; Andrus, Linda; Ding, Wenge; Jiang, Xinpei; Learn, Gerald H.; von Schaewen, Markus; Wen, Jessica; Goepfert, Paul A.; Hahn, Beatrice H.; Ploss, Alexander; Rice, Charles M.

    2015-01-01

    ABSTRACT Hepatitis C virus (HCV) infection is characterized by persistent replication of a complex mixture of viruses termed a “quasispecies.” Transmission is generally associated with a stringent population bottleneck characterized by infection by limited numbers of “transmitted/founder” (T/F) viruses. Characterization of T/F genomes of human immunodeficiency virus type 1 (HIV-1) has been integral to studies of transmission, immunopathogenesis, and vaccine development. Here, we describe the identification of complete T/F genomes of HCV by single-genome sequencing of plasma viral RNA from acutely infected subjects. A total of 2,739 single-genome-derived amplicons comprising 10,966,507 bp from 18 acute-phase and 11 chronically infected subjects were analyzed. Acute-phase sequences diversified essentially randomly, except for the poly(U/UC) tract, which was subject to polymerase slippage. Fourteen acute-phase subjects were productively infected by more than one genetically distinct virus, permitting assessment of recombination between replicating genomes. No evidence of recombination was found among 1,589 sequences analyzed. Envelope sequences of T/F genomes lacked transmission signatures that could distinguish them from chronic infection viruses. Among chronically infected subjects, higher nucleotide substitution rates were observed in the poly(U/UC) tract than in envelope hypervariable region 1. Fourteen full-length molecular clones with variable poly(U/UC) sequences corresponding to seven genotype 1a, 1b, 3a, and 4a T/F viruses were generated. Like most unadapted HCV clones, T/F genomes did not replicate efficiently in Huh 7.5 cells, indicating that additional cellular factors or viral adaptations are necessary for in vitro replication. Full-length T/F HCV genomes and their progeny provide unique insights into virus transmission, virus evolution, and virus-host interactions associated with immunopathogenesis. PMID:25714714

  8. Jean-Martin Charcot and art: relationship of the "founder of neurology" with various aspects of art.

    PubMed

    Bogousslavsky, Julien; Boller, François

    2013-01-01

    Jean-Martin Charcot (1825-1893), the "father of neurology" in France and much beyond, was also the man who established academic psychiatry in Paris, differentiating it from clinical alienism. In his teaching, he used artistic representations from previous centuries to illustrate the historical developments of hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw portraits (in particular, sketches of colleagues during boring faculty meetings and students' examinations), caricatures of himself and others, church sculptures, landscapes, soldiers, etc. He also used this skill in his clinical and scientific work; he drew histological or anatomic specimens, as well as patients' features and demeanor. His most daring artistic experiments were drawing under the influence of hashish. Charcot's tastes in art were conservative; he displayed no affinity for the avant-gardes of his time, including impressionism, or for contemporary musicians, such as César Franck or Hector Berlioz. Léon Daudet, son of Charcot's former friend and famous writer Alphonse Daudet, described Charcot's home as a pseudo-gothic kitsch accumulation of heteroclite pieces of furniture and materials. However, as Henry Meige wrote a few years after his mentor's death, Charcot the artist remains "inseparable from Charcot the physician." PMID:24041281

  9. Genetic Linkage Mapping and Segregation Distortion in a Three-Generation Four-Founder Population of Panicum vigatum (L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Switchgrass (Panicum virgatum L.), a warm season, C4, perennial grass, is one of the predominant grass species of the North American tall grass prairies. It is viewed as a high-potential bioenergy feedstock species because it can produce large amounts of lignocellulosic material with relatively few ...

  10. Anatomy of the eye from the view of Ibn Al-Haitham (965-1039). The founder of modern optics.

    PubMed

    Unal, Nedim; Elcioglu, Omur

    2009-03-01

    Ibn Al-Haitham (known as Alhazen in Latin [965 Basra, Iraq-1039, Cairo, Egypt]) was a scientist who played an important role in the middle age Islam world. He wrote many books and novels, but only 90 of them are known. His main book Kitab al-Manazir was translated into Western languages in the late twelfth century, and in the early thirteenth century. In this book, he formulated many hypotheses on optical science. The book, which is also known as Optic treasure (opticae thesaurus), affected many famous Western scientists. He became an authority until the seventeenth century in the Eastern and Western countries. Roger Bacon (1212-1294), who made radical changes in the Western optical traditions, reconfirmed Ibn Al-Haitham's findings. Ibn al-Haitham began his book Kitab al-Manazir with the anatomy and physiology of the eye. He specifically described cornea, humor aqueous, lens, and corpus vitreum. He examined the effect of light on seeing. He caused changes in the prevailing ideas of his age, and suggested that light came from objects, not from the eye. He provided information regarding the optic nerve, retina, iris, and conjunctiva. He showed the system of the eye as a dioptric, and the relations between the parts of the eye. It is understood that he mastered all knowledge on the structure of the eye in his century. The best proof of this is the eye picture that he drew.

  11. Jean-Martin Charcot and art: relationship of the "founder of neurology" with various aspects of art.

    PubMed

    Bogousslavsky, Julien; Boller, François

    2013-01-01

    Jean-Martin Charcot (1825-1893), the "father of neurology" in France and much beyond, was also the man who established academic psychiatry in Paris, differentiating it from clinical alienism. In his teaching, he used artistic representations from previous centuries to illustrate the historical developments of hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw portraits (in particular, sketches of colleagues during boring faculty meetings and students' examinations), caricatures of himself and others, church sculptures, landscapes, soldiers, etc. He also used this skill in his clinical and scientific work; he drew histological or anatomic specimens, as well as patients' features and demeanor. His most daring artistic experiments were drawing under the influence of hashish. Charcot's tastes in art were conservative; he displayed no affinity for the avant-gardes of his time, including impressionism, or for contemporary musicians, such as César Franck or Hector Berlioz. Léon Daudet, son of Charcot's former friend and famous writer Alphonse Daudet, described Charcot's home as a pseudo-gothic kitsch accumulation of heteroclite pieces of furniture and materials. However, as Henry Meige wrote a few years after his mentor's death, Charcot the artist remains "inseparable from Charcot the physician."

  12. I. P. Pavlov and W. B. Cannon: founders of modern physiological thought relative to behavior and the autonomic nervous system.

    PubMed

    Brooks, C M

    1985-01-01

    It was almost a half century ago that I last attended an International Congress in Moscow and Leningrad--the IUPS Congress of 1935. My wife and I traveled far and saw the majesty of this land and its peoples. Here I met the great Pavlov and heard him present his thoughts concerning the conditioning of behavior. Cannon presented his concepts of transmitters and receptors. There were many other famous physiologists present, A. V. Hill and Lord Adrian; Kato of Japan demonstrated single nerve fiber studies. Someone talked of conditioned diuresis; I read a paper on hypothalamic control of the hypophysis. That was the dawn of neuroendocrinology, studies of hypothalamic function, sensory receptors, and the transmitter-receptor era. It was, like now, a time of great scientific endeavor, but there were clouds in the sky--Stalin and Hitler were coming to power, but the U.S.S.R. and America were friends, and in science it is still so. I wonder what some young man here will be able to report 50 years from now.

  13. The first Nobel Peace Prize, Henry Dunant (founder of the International Red Cross) and his "Mémoirs".

    PubMed

    Ottaviani, Raimonda; Vanni, Paolo; Baccolo, Grazia M; Guerin, Elizabeth; Vanni, Duccio

    2003-06-01

    To celebrate the memory and work of Henry Dunant, on the centenary of the presentation of the first Nobel Peace Prize, rightly awarded to Dunant for his having founded the institution of the International Red Cross, this paper presents the reader with some insights into his activities and sufferings, his trials and tribulations, and the hope and strength of his character. The ceaseless efforts made by Dunant to bring about the Institution which today represents Hope for so many suffering people who are silent victims of wars and atrocities, are fleetingly presented. The authors' intention is to give due recognition to Dunant for his work, and to highlight the humanity and the moral and social worth of the face behind the International Red Cross.

  14. A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies

    PubMed Central

    Shaheen, Ranad; Schmidts, Miriam; Faqeih, Eissa; Hashem, Amal; Lausch, Ekkehart; Holder, Isabel; Superti-Furga, Andrea; Mitchison, Hannah M.; Almoisheer, Agaadir; Alamro, Rana; Alshiddi, Tarfa; Alzahrani, Fatma; Beales, Philip L.; Alkuraya, Fowzan S.

    2015-01-01

    Jeune asphyxiating thoracic dystrophy (JATD) is a skeletal dysplasia characterized by a small thoracic cage and a range of skeletal and extra-skeletal anomalies. JATD is genetically heterogeneous with at least nine genes identified, all encoding ciliary proteins, hence the classification of JATD as a skeletal ciliopathy. Consistent with the observation that the heterogeneous molecular basis of JATD has not been fully determined yet, we have identified two consanguineous Saudi families segregating JATD who share a single identical ancestral homozygous haplotype among the affected members. Whole-exome sequencing revealed a single novel variant within the disease haplotype in CEP120, which encodes a core centriolar protein. Subsequent targeted sequencing of CEP120 in Saudi and European JATD cohorts identified two additional families with the same missense mutation. Combining the four families in linkage analysis confirmed a significant genome-wide linkage signal at the CEP120 locus. This missense change alters a highly conserved amino acid within CEP120 (p.Ala199Pro). In addition, we show marked reduction of cilia and abnormal number of centrioles in fibroblasts from one affected individual. Inhibition of the CEP120 ortholog in zebrafish produced pleiotropic phenotypes characteristic of cilia defects including abnormal body curvature, hydrocephalus, otolith defects and abnormal renal, head and craniofacial development. We also demonstrate that in CEP120 morphants, cilia are shortened in the neural tube and disorganized in the pronephros. These results are consistent with aberrant CEP120 being implicated in the pathogenesis of JATD and expand the role of centriolar proteins in skeletal ciliopathies. PMID:25361962

  15. Stochastic changes over time and not founder effects drive cage effects in microbial community assembly in a mouse model

    PubMed Central

    McCafferty, Jonathan; Mühlbauer, Marcus; Gharaibeh, Raad Z; Arthur, Janelle C; Perez-Chanona, Ernesto; Sha, Wei; Jobin, Christian; Fodor, Anthony A

    2013-01-01

    Maternal transmission and cage effects are powerful confounding factors in microbiome studies. To assess the consequences of cage microenvironment on the mouse gut microbiome, two groups of germ-free (GF) wild-type (WT) mice, one gavaged with a microbiota harvested from adult WT mice and another allowed to acquire the microbiome from the cage microenvironment, were monitored using Illumina 16S rRNA sequencing over a period of 8 weeks. Our results revealed that cage effects in WT mice moved from GF to specific pathogen free (SPF) conditions take several weeks to develop and are not eliminated by the initial gavage treatment. Initial gavage influenced, but did not eliminate a successional pattern in which Proteobacteria became less abundant over time. An analysis in which 16S rRNA sequences are mapped to the closest sequenced whole genome suggests that the functional potential of microbial genomes changes significantly over time shifting from an emphasis on pathogenesis and motility early in community assembly to metabolic processes at later time points. Functionally, mice allowed to naturally acquire a microbial community from their cage, but not mice gavaged with a common biome, exhibit a cage effect in Dextran Sulfate Sodium-induced inflammation. Our results argue that while there are long-term effects of the founding community, these effects are mitigated by cage microenvironment and successional community assembly over time, which must both be explicitly considered in the interpretation of microbiome mouse experiments. PMID:23823492

  16. Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutation.

    PubMed

    Rodríguez-Martínez, Ana B; Alfonso-Sánchez, Miguel A; Peña, José A; Sánchez-Valle, Raquel; Zerr, Inga; Capellari, Sabina; Calero, Miguel; Zarranz, Juan J; de Pancorbo, Marian M

    2008-05-01

    This work presents a detailed investigation of the genomic region surrounding the PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI) from several European countries, notably Spain. The main focus of the study was to explore the origins of the chromosomes carrying the D178N mutation by designing a single-nucleotide polymorphism (SNP) haplotype around the PRNP gene. Haplotypes were constructed by genotyping six SNPs (rs2756271, rs13040327, rs6037932, rs13045348, rs6116474, and rs6116475) in 25 FFI patients from all over Spain. To augment the geographical scope of our study, 13 further FFI cases from Germany (9) and Italy (4) were also examined. Genotyping of SNPs in conjunction with the analysis of genealogical data for a group of FFI patients revealed the existence of two distinct haplotypes potentially associated with the D178N mutation. Of them, GCATTA-M proved to be the common haplotype of Spanish patients, whereas ACATTA-M was typical of the German cases. It is interesting to note that both haplotypes were identified in the Italian samples: GCATTA-M in a family from the Tuscany region and ACATTA-M in a family from the Veneto region. Our findings suggest the occurrence of two independent D178N-129M mutational events in Europe, preserved and transmitted from one generation to the next until nowadays. Likewise, results based on the analysis of SNP data indicate that previous hypotheses postulating that the D178N mutation had independent origins for each family and that its global distribution was determined by recurrent mutational events must be regarded with caution.

  17. From patient to discoverer--Niels Ryberg Finsen (1860–1904) --the founder of phototherapy in dermatology.

    PubMed

    Grzybowski, Andrzej; Pietrzak, Krzysztof

    2012-01-01

    Niels Ryberg Finsen (1860–1904) developed a lamp based on electric carbon arcs (later known as the Finsen light) that was used for skin therapy a century ago. He became director of the Medical Light Institute in Copenhagen, later the Finsen Institute, where he developed this method of treatment. Within a few years, 40 Finsen Institutes were established in Europe and in the United States of America. In 1903, Finsen received the Nobel Prize in Medicine in recognition of his work on the treatment of diseases and, in particular, the treatment of lupus vulgaris by means of concentrated light rays. Finsen's scientific interests were greatly influenced by his health condition. Beginning in 1883, he began to experience symptoms of an illness that would be later diagnosed as Niemann-Pick disease. He spent the last years of his life confined to a wheelchair. Dermatology reaps the benefits of light treatment to this day.

  18. Why Traditional Expository Teaching-Learning Approaches May Founder? An Experimental Examination of Neural Networks in Biology Learning

    ERIC Educational Resources Information Center

    Lee, Jun-Ki; Kwon, Yong-Ju

    2011-01-01

    Using functional magnetic resonance imaging (fMRI), this study investigates and discusses neurological explanations for, and the educational implications of, the neural network activations involved in hypothesis-generating and hypothesis-understanding for biology education. Two sets of task paradigms about biological phenomena were designed:…

  19. A founder EIF2AK4 mutation causes an aggressive form of pulmonary arterial hypertension in Iberian Gypsies.

    PubMed

    Tenorio, J; Navas, P; Barrios, E; Fernández, L; Nevado, J; Quezada, C A; López-Meseguer, M; Arias, P; Mena, R; Lobo, J L; Alvarez, C; Heath, K; Escribano-Subías, P; Lapunzina, P

    2015-12-01

    Pulmonary arterial hypertension (PAH) is a pathological condition characterized by a persistent and progressive elevation of pulmonary vascular resistance with devastating consequences if untreated. In the past recent years, several genes have been related to PAH, however, the molecular defect remains unknown in a significant proportion of patients with familial PAH (∼20%). During the past few years, we have observed that PAH shows a particular behavior in Iberian Gypsies, with more aggressive course and frequently affecting multiple members of the same family. We studied five Gypsy families in whom at least one individual from each family developed a severe form of PAH and in whom no mutation had been identified in the common genes. We applied SNP-array-based homozygosity mapping in three families and obtained, among others, one of which included the gene EIF2AK4, recently reported in patients with PAH from group-1' pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH). Subsequently, we sequenced EIF2AK4 and found a homozygous mutation in all five families: c.3344C>T(p.P1115L). The majority of our patients required early lung transplantation. Hence, this mutation appeared with a more severe phenotype than previously reported for other EIF2AK4 mutations. The finding of this novel mutation is important for genetic counseling and calculation of population recurrence risks.

  20. Impact of historical founder effects and a recent bottleneck on MHC variability in Commander Arctic foxes (Vulpes lagopus)

    PubMed Central

    Ploshnitsa, Anna I; Goltsman, Mikhail E; Macdonald, David W; Kennedy, Lorna J; Sommer, Simone

    2012-01-01

    Populations of Arctic foxes (Vulpes lagopus) have been isolated on two of the Commander Islands (Bering and Mednyi) from the circumpolar distributed mainland population since the Pleistocene. In 1970–1980, an epizootic outbreak of mange caused a severe population decline on Mednyi Island. Genes of the major histocompatibility complex (MHC) play a primary role in infectious disease resistance. The main objectives of our study were to compare contemporary variation of MHC class II in mainland and island Arctic foxes, and to document the effects of the isolation and the recent bottleneck on MHC polymorphism by analyzing samples from historical and contemporary Arctic foxes. In 184 individuals, we found 25 unique MHC class II DRB and DQB alleles, and identified evidence of balancing selection maintaining allelic lineages over time at both loci. Twenty different MHC alleles were observed in mainland foxes and eight in Bering Island foxes. The historical Mednyi population contained five alleles and all contemporary individuals were monomorphic at both DRB and DQB. Our data indicate that despite positive and diversifying selection leading to elevated rates of amino acid replacement in functionally important antigen-binding sites, below a certain population size, balancing selection may not be strong enough to maintain genetic diversity in functionally important genes. This may have important fitness consequences and might explain the high pathogen susceptibility in some island populations. This is the first study that compares MHC diversity before and after a bottleneck in a wild canid population using DNA from museum samples. PMID:22408734

  1. Sir James Edward Smith (1759-1828) MD FRS, botanist, co-founder of the Linnean Society of London.

    PubMed

    Hawgood, Barbara J

    2009-05-01

    James Edward Smith's interest in botany led him to enter medicine at Edinburgh in 1781. Smith was continuing his medical studies in London when Sir Joseph Banks (1743-1820) suggested to him that he should purchase the collection of the famous Swedish naturalist Carl Linnaeus that had just been offered to Banks. Smith bought the Linnean Collection and Library in 1784. In 1786 he was awarded the degree of Doctor of Medicine from Leiden. In 1788 Smith, with two associates, founded the Linnean Society of London and became President for life. Smith turned from medicine to natural history as a lecturer and writer. During his lifetime he produced numerous botanical works of high value, including The English Flora (1824-28), and he did much to popularize botany.

  2. The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel

    PubMed Central

    Vazina, A; Baniel, J; Yaacobi, Y; Shtriker, A; Engelstein, D; Leibovitz, I; Zehavi, M; Sidi, A A; Ramon, Y; Tischler, T; Livne, P M; Friedman, E

    2000-01-01

    Inherited predisposition occurs in 5–10% of all prostate cancer (CaP) patients, but the genes involved in conferring genetic susceptibility remain largely unknown. Several lines of evidence indicate that germline mutations in BRCA1 and BRCA2 might be associated with an increased risk for CaP. Three mutations in these two genes (185delAG and 5382InsC (BRCA1) and 6174delT (BRCA2) occur in about 2.5% of the general Ashkenazi population, and the 185delAG BRCA1 mutation, in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these germline mutations to prostate cancer in Jewish Israeli patients, we tested 174 unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations by PCR amplification and modified restriction enzyme digests. Patient’s age range was 45–81 years (median 66), and in 24 (14.4%) the disease was diagnosed prior to 55 years of age. Nineteen (11%) and 12 (6.9%) patients had a first or second degree relative with CaP or breast cancer, respectively. Overall, five mutation carriers were detected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158 (0.6%) 6174delT. In all carriers, the disease was diagnosed after the age of 55, and only one of them had a family history of breast and CaP. In addition, no allelic losses at the BRCA1 locus were demonstrated in 17 patients with a family history of CaP, using seven microsatellite markers. We conclude that the rate of the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients does not significantly differ from that of the general population, and that mutational inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2 mutations probably contribute little to CaP occurrence, to inherited predisposition, and to early onset disease in Jewish individuals. © 2000 Cancer Research Campaign PMID:10945492

  3. On the Number of New World Founders: A Population Genetic Portrait of the Peopling of the Americas

    PubMed Central

    2005-01-01

    The founding of New World populations by Asian peoples is the focus of considerable archaeological and genetic research, and there persist important questions on when and how these events occurred. Genetic data offer great potential for the study of human population history, but there are significant challenges in discerning distinct demographic processes. A new method for the study of diverging populations was applied to questions on the founding and history of Amerind-speaking Native American populations. The model permits estimation of founding population sizes, changes in population size, time of population formation, and gene flow. Analyses of data from nine loci are consistent with the general portrait that has emerged from archaeological and other kinds of evidence. The estimated effective size of the founding population for the New World is fewer than 80 individuals, approximately 1% of the effective size of the estimated ancestral Asian population. By adding a splitting parameter to population divergence models it becomes possible to develop detailed portraits of human demographic history. Analyses of Asian and New World data support a model of a recent founding of the New World by a population of quite small effective size. PMID:15898833

  4. The genome-wide landscape of copy number variations in the MUSGEN study provides evidence for a founder effect in the isolated Finnish population

    PubMed Central

    Kanduri, Chakravarthi; Ukkola-Vuoti, Liisa; Oikkonen, Jaana; Buck, Gemma; Blancher, Christine; Raijas, Pirre; Karma, Kai; Lähdesmäki, Harri; Järvelä, Irma

    2013-01-01

    Here we characterized the genome-wide architecture of copy number variations (CNVs) in 286 healthy, unrelated Finnish individuals belonging to the MUSGEN study, where molecular background underlying musical aptitude and related traits are studied. By using Illumina HumanOmniExpress-12v.1.0 beadchip, we identified 5493 CNVs that were spread across 467 different cytogenetic regions, spanning a total size of 287.83 Mb (∼9.6% of the human genome). Merging the overlapping CNVs across samples resulted in 999 discrete copy number variable regions (CNVRs), of which ∼6.9% were putatively novel. The average number of CNVs per person was 20, whereas the average size of CNV per locus was 52.39 kb. Large CNVs (>1 Mb) were present in 4% of the samples. The proportion of homozygous deletions in this data set (∼12.4%) seemed to be higher when compared with three other populations. Interestingly, several CNVRs were significantly enriched in this sample set, whereas several others were totally depleted. For example, a CNVR at chr2p22.1 intersecting GALM was more common in this population (P=3.3706 × 10−44) than in African and other European populations. The enriched CNVRs, however, showed no significant association with music-related phenotypes. Moreover, the most common CNV locations in world's normal population cohorts (6q14.1, 11q11) were overrepresented in this population. Thus, the genome-wide CNV investigation in this Finnish sample set demonstrated features that are characteristic to isolated populations. Novel CNVRs and the functional implications of CNVs revealed in this study elucidate structural variation present in this population isolate, and may also serve as candidate gene loci for music-related traits. PMID:23591402

  5. A recurrent homozygous nonsense mutation within the LAMA3 gene as a cause of Herlitz junctional epidermolysis bullosa in patients of Pakistani ancestry: evidence for a founder effect.

    PubMed

    McGrath, J A; Kivirikko, S; Ciatti, S; Moss, C; Christiano, A M; Uitto, J

    1996-04-01

    The anchoring filament protein laminin 5 is abnormally expressed in the skin of patients with Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a H-JEB child of first-cousin Pakistani parents, and identified a homozygous C-to-T transition in the LAMA3 gene of laminin 5 resulting in a premature termination codon (CGA-TGA) on both alleles. This mutation, R650X, has been previously reported in two other seemingly unrelated H-JEB individuals of Pakistani ancestry. Although this mutation may represent a mutational hotspot within the LAMA3 gene, haplotype analysis based on a silent intragenic polymorphism (GCC/GCG, alanine 429; GenBank no. L34155), and on three flanking microsatellite polymorphism (D18S45, D18S478, and D18S480), suggests that a common ancestral allele may be present in all three cases. PMID:8618022

  6. Haplotype and quantitative transcript analyses of Portuguese breast/ovarian cancer families with the BRCA1 R71G founder mutation of Galician origin.

    PubMed

    Santos, Catarina; Peixoto, Ana; Rocha, Patrícia; Vega, Ana; Soares, Maria José; Cerveira, Nuno; Bizarro, Susana; Pinheiro, Manuela; Pereira, Deolinda; Rodrigues, Helena; Castro, Fernando; Henrique, Rui; Teixeira, Manuel R

    2009-01-01

    We investigated the functional effect of the missense variant c.211A>G (R71G) localized at position -2 of exon 5 donor splice site in the BRCA1 gene and evaluated whether Portuguese and Galician families with this mutation share a common ancestry. Three unrelated Portuguese breast/ovarian cancer families carrying this variant were studied through qualitative and quantitative transcript analyses. We also evaluated the presence of loss of heterozigosity and the histopathologic characteristics of the carcinomas in those families. Informative families (two from Portugal and one from Galicia) were genotyped for polymorphic microsatellite markers flanking BRCA1 to reconstruct haplotypes. Qualitative RNA analysis revealed the presence of two alternative transcripts both in carriers of the BRCA1 R71G variant and in controls. Semi-quantitative fragment analysis and real-time RT-PCR showed a significant increase of the transcript with an out of frame deletion of the last 22nt of exon 5 (BRCA1-Delta22ntex5) and a decrease of the full-length transcript (BRCA1-ex5FL) in patients carrying the R71G mutation as compared to controls, whereas no significant differences were found for the transcript with in frame skipping of exon 5 (BRCA1-Deltaex5). One haplotype was found to segregate in the two informative Portuguese families and in the Galician family. We demonstrate that disruption of alternative transcript ratios is the mechanism causing hereditary breast/ovarian cancer associated with the BRCA1 R71G mutation. Furthermore, our findings indicate a common ancestry of the Portuguese and Galician families sharing this mutation. PMID:19123044

  7. Annotation of long non-coding RNAs expressed in Collaborative Cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts

    PubMed Central

    Josset, Laurence; Tchitchek, Nicolas; Gralinski, Lisa E; Ferris, Martin T; Eisfeld, Amie J; Green, Richard R; Thomas, Matthew J; Tisoncik-Go, Jennifer; Schroth, Gary P; Kawaoka, Yoshihiro; Pardo-Manuel de Villena, Fernando; Baric, Ralph S; Heise, Mark T; Peng, Xinxia; Katze, Michael G

    2014-01-01

    The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb). PMID:24922324

  8. Evidence for a founder effect for the IVS4 +4 A{r_arrow}T mutation in the Fanconi anemia gene FACC in a Jewish population

    SciTech Connect

    Verlander, P.C.; Kaporis, A.G.; Qian, L.

    1994-09-01

    Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder defined by hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C(FACC) has been cloned. Two common mutations, IVS4 +4 A{r_arrow}T and 322delG, and several rare mutations have recently been reported in affected individuals. We now report the development of amplification refractory mutation system (ARMS) assays for rapid, non-radioactive detection of these known mutations in FACC. Primer pairs specific for variant sequences were designed, with the 3{prime} terminal base of one primer matching the variant base. PCR products are separated by electrophoresis on 2.5% agarose gels; mutations are indicated by the presence of a band of a specific size. These ARMS assays can be multiplexed to allow screening for all known mutations in two PCR reactions. We have used these assays for detection of FACC mutations in affected individuals in the International Fanconi Anemia Registry (IFAR), and for carrier detection FACC families. IVS4 +4 A{r_arrow}T is the only FACC mutation found in Jewish FA patients and their families, of both Ashkenazi and Sephardic ancestry. This mutation was not found in any affected individual of non-Jewish origin. In addition, DNA samples from 1596 healthy Jewish individuals primarily of Ashkenazi ancestry were supplied to us by Dor Yeshorim. These samples, ascertained for carrier screening for Tay Sachs, cystic fibrosis, and other genetic diseases with a high frequency in the religious Jewish community served by this organization, were tested for both IVS4 +4 A{r_arrow}T and 322delG mutations; seventeen IVS4 +4 A{r_arrow}T are of Sephardic Jewish ancestry. We hypothesize that IVS4 +4 A{r_arrow}T is a very old mutation, predating the divergence of the Ashkenazi and Sephardic populations. Haplotype analysis with microsatellite markers is in progress.

  9. Middle Cambrian to Late Ordovician evolution of the Appalachian margin: Foundering of a passive margin to form a subduction zone and volcanic arc

    SciTech Connect

    Washington, P.A. , Southern Pines, NC )

    1994-03-01

    From late Middle Cambrian to early Late Ordovician time, the Appalachian passive margin experienced a series of orogenic events culminating in the Taconic orogeny. Most of these events are generally viewed as enigmatic and isolated, but they can be viewed as a coherent tectonic sequence of events. The early stages involved broad uplifts and localized extension, especially of internal shelf and adjacent continental interiors. Later stages involved increased subsidence rates of the outer shelf, resulting in retreat of the outer margin of the carbonate platform.The beginning of volcanic activity coincides with, or immediately follows, the rapid subsidence. Onset of compressional orogenesis is often temporally separated from the initial rapid subsidence. These events can be integrated into a tectonic model in which the passive margin is converted into an active Andean margin. Early uplift and extension events represented the surface expression of the beginning of deep-seated downward mantle convection. Subsequent rapid subsidence events represented the mechanical failure of the lithosphere as the convection reaches maturity. Failure of the lithosphere resulted in a subduction zone that quickly created arc volcanism. The compressive Taconic orogenesis occurred when the arc was thrust back onto the shelf margin as the subduction zone migrated continentward in response to progressively channeled convective flow.

  10. Thomas Henry Osler (1875-1936): a descendant of Sir William Osler's great-uncle and the founder of a South African medical dynasty.

    PubMed

    Myers, Edward D

    2009-08-01

    Sir William Osler's great-uncle Benjamin emigrated from England to South Africa with his wife and children in 1820. From Benjamin's son, Stephen, descended a large family of Oslers including at least seven doctors and dentists. This paper describes the lives and careers of Thomas Henry, and his medical and dental descendants. PMID:19723960

  11. Inferential Genotyping of Y Chromosomes in Latter-Day Saints Founders and Comparison to Utah Samples in the HapMap Project

    PubMed Central

    Gitschier, Jane

    2009-01-01

    One concern in human genetics research is maintaining the privacy of study participants. The growth in genealogical registries may contribute to loss of privacy, given that genotypic information is accessible online to facilitate discovery of genetic relationships. Through iterative use of two such web archives, FamilySearch and Sorenson Molecular Genealogy Foundation, I was able to discern the likely haplotypes for the Y chromosomes of two men, Joseph Smith and Brigham Young, who were instrumental in the founding of the Latter-Day Saints Church. I then determined whether any of the Utahns who contributed to the HapMap project (the “CEU” set) is related to either man, on the basis of haplotype analysis of the Y chromosome. Although none of the CEU contributors appear to be a male-line relative, I discovered that predictions could be made for the surnames of the CEU participants by a similar process. For 20 of the 30 unrelated CEU samples, at least one exact match was revealed, and for 17 of these, a potential ancestor from Utah or a neighboring state could be identified. For the remaining ten samples, a match was nearly perfect, typically deviating by only one marker repeat unit. The same query performed in two other large databases revealed fewer individual matches and helped to clarify which surname predictions are more likely to be correct. Because large data sets of genotypes from both consenting research subjects and individuals pursuing genetic genealogy will be accessible online, this type of triangulation between databases may compromise the privacy of research subjects. PMID:19215731

  12. PAPERS ON THE MATHEMATICAL ACTIVITY OF R.L. DOBRUSHIN: R.L. Dobrushin - one of the founders of modern mathematical physics

    NASA Astrophysics Data System (ADS)

    Minlos, R. A.

    1997-04-01

    Contents §1. Phase transitions §2. Gibbsian random fields (the DLR-definition and everything about it) §3. Markov processes with local interaction §4. The Wulff construction and the theory of large deviations in a two-phase region Bibliography

  13. [Eugène-Humbert Guitard, 1884-1976, initiator of the Société d' histoire de la pharmacie and founder of its bulletin].

    PubMed

    Julien, Pierre

    2003-01-01

    In 1913, the year when he publishes Deux siècles de presse au service de la pharmacie et cinquante ans de < L' Union pharmaceutique >, Guitard creates the < Société d' histoire de la pharmacie > (he is its genuine father, and not Charles Buchet) and starts its Bulletin (subsequently Revue) the editorship of which he will handle half a century. The author focuses on the striking features of his outstanding personality (acchivist, librarian, curator of a museum, expert at writing, bookseller, printer and publisher, hellenist, professor of history of pharmacy, journalist, columnist, musician, art-lover, urbanist, active defender of our cultural legacy) and the remarkable qualities of his four great works of history of pharmacy.

  14. [Outstanding scientist-investigator, S. S. Brukhonenko--founder of artificial circulation method and developer of first in the world autoejector].

    PubMed

    Pavlovskiĭ, L N

    2009-01-01

    The article presents data about well-known Russian physician-physiologist and researcher Sergey Sergeeviche Brukhonenko. The hard way passed by the scientist-researcher from completion of artificial breath technique to the method of artificial blood circulation developed by him and development of the first in the world--artificial blood circulation device--autoejector is shown in the article.

  15. [Dr. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements. Part 4: Prof. M. Matsuoka's lecture to medical and civic communities].

    PubMed

    Hirotani, Hayato

    2010-03-01

    Dr. M. Matsuoka gave many lectures to physicians at the Postdoctoral Course Lectures sponsored by the Kyoto Eisei Kensasho (Kyoto Bacterial and Biochemical Laboratory) run by the Kyoto Medical Association, and the Postdoctoral Course Lectures of the Kyoto Medical School, Kyoto Imperial University. He was also invited to give lectures at several regional medical associations. He also was a speaker at the Kyoto Imperial University Extension course and he lectured at the Enryakuji Temple on Mt. Hiei, sponsored by a newspaper company. It is remarkable that these activities were carried out in addition to his other notable academic work previously reported.

  16. The application of business models to medical research: interviews with two founders of directed-philanthropy foundations. Interview with Scott Johnson and Don Listwin by Kathryn A. Phillips.

    PubMed

    Scott, Johnson; Listwin, Don

    2007-01-01

    A new trend in research funding has emerged: directed philanthropy, in which the donor plays an active, hands-on role in managing the research by applying a "business model." Although such efforts now represent only a small portion of foundation funding, they have potentially far-reaching implications because (1) the approach of using a business model is being applied more broadly and (2) the success or failure of these efforts may portend the fate of larger translational efforts. The author conducted interviews with Scott Johnson of the Myelin Repair Foundation and Don Listwin of the Canary Foundation in the fall of 2006.

  17. One hundred years since the birth of academician Dimitar Arsov, founder and nestor of the modern internal medicine in the Republic of Macedonia.

    PubMed

    Polenaković, M

    2013-01-01

    Dimitar Arsov was born in Kriva Palanka on September 28, 1908 and died on July 2, 1974 in Skopje; he had finished elementary education in Kriva Palanka, high school (1922-1926) in Kumanovo, Macedonia and Col-lege of Medicine (1926-1932), Ph. D. University of Paris, Sorbone, France, 1936. He returned to Macedonia in 1937. In 1947 he was elected and Assistant Professor and in 1950 a Docent at the Faculty of Medicine in Skopje. He was appointed Director of the Clinic of Medicine and Head of the Chair of Internal Medicine, who served at those positions in the period 1952-74. In 1958 he was elected Professor of Internal Medicine. The first habilitation of the Medical Faculty in Skopje was defended by D. Arsov in 1954, titled: "The Effects of the Intravenous Epinephrine on the Hypersplenism of Malaria and Cala-Azar". On August 18, 1967, D. Arsov was elected Full Member and also the first member in the field of medicine of the Macedonian Academy of Sciences and Arts. The excellent experience in the work with the patients, precise observation of the symptoms and syndromes of the diseases in each patient, knowing the most advanced therapy at that time enabled D. Arsov to make conclusion for possibility of new therapy and gave him the material for writing scientific papers. In the first half of the 50s, during his regular work, Arsov discovers a new, internationally recognized therapy for rheumatism. Patients of both Cala-Azar and inflammatory rheumatism were treated with small doses of adrenaline therapy and they felt drastic decrease in rheumatism inflammation within one week. This therapy was used a couple of years in several countries around the world. He participated in the undergraduate and graduate studies. He contributed to the development of 2,240 graduated doctors and under his management over 300 doctors specialized in internal medicine and became specialists internists. Under his management, numerous habilitations and dissertations in internal medicine were finished. He contributed also to the development of 25 assistants, 5 docents, 5 full-time professors in internal medicine at the Medical Faculty in Skopje. He has published more than 200 papers from different areas of internal medicine, of which 36 are on the PubMed. He has published 5 books on internal medicine for students and doctors. He was a President and member of several Macedonian medical associations, as well as of medical associations of former Yugoslavia. He was awarded with the highest awards of former Yugoslavia and Macedonia. He was also awarded with international awards, such as: Doctor Honoris Causa by the University in Besancon and Honor and Medal from the City Assembly of Besancon (France). During his management of the Internal clinic the University Internal clinic developed eight different sub-specialist departments: Cardiology, Pneumology, Rheumatology, Nephrology, Hematology, Gastroenterology and Endocrinology with metabolism and Clinical biochemical laboratory. The fast development of subspecialties has led to development of separate clinics for each subspecialty in 1975, so only the Chair of Internal Medicine remained as a connection between the subspecialties for education and scientific research. He was a prolific scientist who after World War II wrote the first scientific and specialist papers and books in the field of internal medicine in Macedonia. He created a school of internal medicine. The scientific and uncompromised attitude towards the expert truth are weaved in the unforgettable face of the Academician Prof. D-r. Dimitar Arsov, scientist, teacher, and doctor. With his vast work in healing the sick and preventing the diseases in the Republic of Macedonia, he became the cornerstone of modern medicine in the Republic of Macedonia. Thus, he truly deserves to be the doyen of internal medicine, one of the leading, most important persons in medicine of the 20th century in our country. Today, his honorary name appears on: Clinic of Rheumatology at the Medical Faculty in Skopje, Medical Center in Kriva Palanka, Scientific Club of the student organization of the Medical Faculty in Skopje.

  18. Lack of founder effect for an identical mtDNA depletion syndrome (MDS)-associated MPV17 mutation shared by Navajos and Italians.

    PubMed

    Spinazzola, Antonella; Massa, Valeria; Hirano, Michio; Zeviani, Massimo

    2008-04-01

    Navajo neurohepatopathy is a hepato-cerebral variant of mitochondrial DNA depletion syndrome due to a specific mutation in MPV17, a gene located on human chromosome 2p. The same mutation was reported in an Italian family. To understand whether the MPV17 mutation was transmitted by descent from a common ancestor to Navajos and Italians we constructed a dense haplotype of the MPV17 locus using suitable single nucleotide polymorphisms. Complete discordance between Italian and Navajo haplotypes rules out the former hypothesis, suggesting that the mutation occurred independently in the two populations. PMID:18261905

  19. Genomes and Characterization of Phages Bcep22 and BcepIL02, Founders of a Novel Phage Type in Burkholderia cenocepacia▿†

    PubMed Central

    Gill, Jason J.; Summer, Elizabeth J.; Russell, William K.; Cologna, Stephanie M.; Carlile, Thomas M.; Fuller, Alicia C.; Kitsopoulos, Kate; Mebane, Leslie M.; Parkinson, Brandi N.; Sullivan, David; Carmody, Lisa A.; Gonzalez, Carlos F.; LiPuma, John J.; Young, Ry

    2011-01-01

    Within the Burkholderia cepacia complex, B. cenocepacia is the most common species associated with aggressive infections in the lungs of cystic fibrosis patients, causing disease that is often refractive to treatment by antibiotics. Phage therapy may be a potential alternative form of treatment for these infections. Here we describe the genome of the previously described therapeutic B. cenocepacia podophage BcepIL02 and its close relative, Bcep22. Phage Bcep22 was found to contain a circularly permuted genome of 63,882 bp containing 77 genes; BcepIL02 was found to be 62,714 bp and contains 76 predicted genes. Major virion-associated proteins were identified by proteomic analysis. We propose that these phages comprise the founding members of a novel podophage lineage, the Bcep22-like phages. Among the interesting features of these phages are a series of tandemly repeated putative tail fiber genes that are similar to each other and also to one or more such genes in the other phages. Both phages also contain an extremely large (ca. 4,600-amino-acid), virion-associated, multidomain protein that accounts for over 20% of the phages' coding capacity, is widely distributed among other bacterial and phage genomes, and may be involved in facilitating DNA entry in both phage and other mobile DNA elements. The phages, which were previously presumed to be virulent, show evidence of a temperate lifestyle but are apparently unable to form stable lysogens in their hosts. This ambiguity complicates determination of a phage lifestyle, a key consideration in the selection of therapeutic phages. PMID:21804006

  20. One hundred years since the birth of academician Dimitar Arsov, founder and nestor of the modern internal medicine in the Republic of Macedonia.

    PubMed

    Polenaković, M

    2013-01-01

    Dimitar Arsov was born in Kriva Palanka on September 28, 1908 and died on July 2, 1974 in Skopje; he had finished elementary education in Kriva Palanka, high school (1922-1926) in Kumanovo, Macedonia and Col-lege of Medicine (1926-1932), Ph. D. University of Paris, Sorbone, France, 1936. He returned to Macedonia in 1937. In 1947 he was elected and Assistant Professor and in 1950 a Docent at the Faculty of Medicine in Skopje. He was appointed Director of the Clinic of Medicine and Head of the Chair of Internal Medicine, who served at those positions in the period 1952-74. In 1958 he was elected Professor of Internal Medicine. The first habilitation of the Medical Faculty in Skopje was defended by D. Arsov in 1954, titled: "The Effects of the Intravenous Epinephrine on the Hypersplenism of Malaria and Cala-Azar". On August 18, 1967, D. Arsov was elected Full Member and also the first member in the field of medicine of the Macedonian Academy of Sciences and Arts. The excellent experience in the work with the patients, precise observation of the symptoms and syndromes of the diseases in each patient, knowing the most advanced therapy at that time enabled D. Arsov to make conclusion for possibility of new therapy and gave him the material for writing scientific papers. In the first half of the 50s, during his regular work, Arsov discovers a new, internationally recognized therapy for rheumatism. Patients of both Cala-Azar and inflammatory rheumatism were treated with small doses of adrenaline therapy and they felt drastic decrease in rheumatism inflammation within one week. This therapy was used a couple of years in several countries around the world. He participated in the undergraduate and graduate studies. He contributed to the development of 2,240 graduated doctors and under his management over 300 doctors specialized in internal medicine and became specialists internists. Under his management, numerous habilitations and dissertations in internal medicine were finished. He contributed also to the development of 25 assistants, 5 docents, 5 full-time professors in internal medicine at the Medical Faculty in Skopje. He has published more than 200 papers from different areas of internal medicine, of which 36 are on the PubMed. He has published 5 books on internal medicine for students and doctors. He was a President and member of several Macedonian medical associations, as well as of medical associations of former Yugoslavia. He was awarded with the highest awards of former Yugoslavia and Macedonia. He was also awarded with international awards, such as: Doctor Honoris Causa by the University in Besancon and Honor and Medal from the City Assembly of Besancon (France). During his management of the Internal clinic the University Internal clinic developed eight different sub-specialist departments: Cardiology, Pneumology, Rheumatology, Nephrology, Hematology, Gastroenterology and Endocrinology with metabolism and Clinical biochemical laboratory. The fast development of subspecialties has led to development of separate clinics for each subspecialty in 1975, so only the Chair of Internal Medicine remained as a connection between the subspecialties for education and scientific research. He was a prolific scientist who after World War II wrote the first scientific and specialist papers and books in the field of internal medicine in Macedonia. He created a school of internal medicine. The scientific and uncompromised attitude towards the expert truth are weaved in the unforgettable face of the Academician Prof. D-r. Dimitar Arsov, scientist, teacher, and doctor. With his vast work in healing the sick and preventing the diseases in the Republic of Macedonia, he became the cornerstone of modern medicine in the Republic of Macedonia. Thus, he truly deserves to be the doyen of internal medicine, one of the leading, most important persons in medicine of the 20th century in our country. Today, his honorary name appears on: Clinic of Rheumatology at the Medical Faculty in Skopje, Medical Center in Kriva Palanka, Scientific Club of the student organization of the Medical Faculty in Skopje. PMID:23928800

  1. Population genetic analysis of microsatellite variation of guppies (Poecilia reticulata) in Trinidad and Tobago: evidence for a dynamic source-sink metapopulation structure, founder events and population bottlenecks.

    PubMed

    Barson, N J; Cable, J; Van Oosterhout, C

    2009-03-01

    Riverine fish populations are traditionally considered to be highly structured and subject to strong genetic drift. Here, we use microsatellites to analyse the population structure of the guppy (Poecilia reticulata), focussing on the headwater floodplain area of the Caroni drainage in Trinidad. We also analyse the population genetics of guppies in the Northern Drainage in Trinidad, a habitat characterized by rivers flowing directly into the sea, and a small isolated population in Tobago. Upland Caroni populations are highly differentiated and display low levels of genetic diversity. However, we found no evidence to suggest that these upland populations experienced recent population crashes and the populations appear to approach mutation-drift equilibrium. Dominant downstream migration over both short- and long-time frames has a strong impact on the population genetics of lowland Caroni populations. This drainage system could be considered a source-sink metapopulation, with the tributary furthest downstream representing a 'super sink', receiving immigrants from rivers upstream in the drainage. Moreover, the effective population size in the lowlands is surprisingly low in comparison with the apparently large census population sizes.

  2. Fine mapping of the gene for carbohydrate-deficient glycoprotein syndrome, type I (CDG1): Linkage disequilibrium and founder effect in Scandinavian families

    SciTech Connect

    Bjursell, C.; Wahlstroem, J.; Martinsson, T.

    1997-02-01

    Carbohydrate-deficient glycoprotein syndrome type I (CDG I) is characterized clinically by severe nervous system involvement and biochemically by defects in the carbohydrate residues in a number of serum glycoproteins. The CDG1 gene was recently localized by us to a 13-cM interval in chromosome region 16p13. In this study 44 CDG I families from nine countries were analyzed with available markers in a region ranging from marker D16S495 to D16S497, and haplotype and linkage disequilibrium analyses were performed. One specific haplotype was found to be markedly overrepresented in CDG I patients from a geographically distinct region in Scandinavia, strongly indicating that CDG I families in this region share the same ancestral CDG1 mutation. Furthermore, analysis of the extent of the common haplotype in these families indicates that the CDG1 gene is located in the region defined by markers D16S513-AFMa284wd5-Dl6S768-Dl6S406-D16S502. The critical CDG1 region, in strong linkage disequilibrium with markers AFMa284wd5, D16S768, and D16S406, thus constitutes less than 1 Mb of DNA and less than 1 cM in the very distal part of the CDG1 region defined by us previously. 14 refs., 3 figs., 2 tabs.

  3. Role of the Alboran Sea volcanic arc choking the Mediterranean to the Messinian salinity crisis and foundering biota diversification in North Africa and Southeast Iberia

    NASA Astrophysics Data System (ADS)

    Booth-Rea, Guillermo; Ranero, Cesar R.; Grevemer, Ingo

    2016-04-01

    The Mediterranean Sea desiccated ~5.96 million years ago when it became isolated from the world oceans during the Messinian salinity crisis. This event permitted the exchange of terrestrial biota between Africa and Iberia contributing to the present rich biodiversity of the Mediterranean region. The cause chocking the Mediterranean has been proposed to be tectonic uplift and dynamic topography but the driving mechanism still remains debated. We present a new wide-angle seismic profile that provides a detailed image of the thickness and seismic velocity distribution of the crust in the eastern Alboran basin. The velocity model shows a characteristic structure of a subduction-related volcanic arc with a high-velocity lower crust and a 16-18 km total-thickness igneous crust that magmatic accreted mostly between ~10-6 Ma across the eastern Alboran basin. Estimation of the isostatically corrected depth of the arc crust taking into account the original thermal structure and sediment-loading subsidence since 6 Ma places a large area of the eastern Alboran basin above sea level at the time. This estimation is supported by geophysical data showing subaereal erosional unconformities for that time. This model may explain several up-to-now-disputed features of the Messinian salinity crisis, including: the progressive isolation of the Mediterranean since 7.1 Ma with the disappearance of open marine taxa, the existence of evaporites mostly to the east of the volcanic arc, the evidence that the Gibraltar straits were not a land bridge offered by continuous Messinian open marine sediments at ODP site 976 in the western Alboran basin, the importance of southeastern Iberia and North Africa as centres of biota diversification since before the salinity crisis, and patterns of speciation irradiating from SE Iberia and the eastern Rif in some taxons.

  4. Type III 3-Methylglutaconic Aciduria (Optic Atrophy Plus Syndrome, or Costeff Optic Atrophy Syndrome): Identification of the OPA3 Gene and Its Founder Mutation in Iraqi Jews

    PubMed Central

    Anikster, Yair; Kleta, Robert; Shaag, Avraham; Gahl, William A.; Elpeleg, Orly

    2001-01-01

    Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) is a neuro-ophthalmologic syndrome that consists of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased. The disorder has been reported in ∼40 patients of Iraqi Jewish origin, allowing the mapping of the disease to chromosome 19q13.2-q13.3, by linkage analysis. To isolate the causative gene, OPA3, we sequenced four genes within the critical interval and identified, in the intronic sequence of a gene corresponding to cDNA clone FLJ22187, a point mutation that segregated with the type III MGA phenotype. The FLJ22187-cDNA clone, which we identified as the OPA3 gene, consists of two exons and encodes a peptide of 179 amino acid residues. Northern blot analysis revealed a primary transcript of ∼5.0 kb that was ubiquitously expressed, most prominently in skeletal muscle and kidney. Within the brain, the cerebral cortex, the medulla, the cerebellum, and the frontal lobe, compared to other parts of the brain, had slightly increased expression. The intronic G→C mutation abolished mRNA expression in fibroblasts from affected patients and was detected in 8 of 85 anonymous Israeli individuals of Iraqi Jewish origin. Milder mutations in OPA3 should be sought in patients with optic atrophy with later onset, even in the absence of additional neurological abnormalities. PMID:11668429

  5. Fidelia Adams Johnson: Ingenious Daughter of the Founder of Grambling State University. From Voices of Inspiration Series, an Oral History Project.

    ERIC Educational Resources Information Center

    Grambling State Univ., LA. Dept. of History and Philosophy.

    In this brief oral history, the life of Fidelia Adams Johnson is recounted with sections devoted to her family background, formative years, college experience, working life and retirement years as a black woman of influence. Her grandfather helped establish Tuskegee Institute and her father founded Louisiana's Grambling State College. Fidelia…

  6. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families

    SciTech Connect

    Friedman, L.S.; Szabo, C.I.; Ostermeyer, E.A.

    1995-12-01

    Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning {approximately}850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset bilateral breast cancer and ovarian cancer to late-onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred independently in two families. In one family, penetrance was complete, with females developing early-onset breast cancer or ovarian cancer and the male carrier developing prostatic cancer, whereas, in the other family, penetrance was incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two novel nonsense mutations led to the loss of mutant BRCA1 transcript in families with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt segment of the BRCA1 3{prime}-UTR and 1.3 kb of genomic sequence including the putative promoter region were invariant by single-strand conformation analysis in 13 families without coding-sequence mutations. Overall in our series, BRCA1 mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7 with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not tested for linkage. Three other families have positive lod scores for linkage to BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores for both BRCA1 and BRCA2. 57 refs., 5 figs., 3 tabs.

  7. The Reality of Aging Viewed from the Arterial Wall: An Interview with Dr. Edward Lakatta, Founder and Director of the Laboratory of Cardiovascular Science, National Institute on Aging.

    PubMed

    Park, Jeong Bae; Park, Sungha

    2013-10-01

    An exclusive interview conducted by Professors Jeong Bae Park and Sungha Park with Dr. Edward Lakatta in Seoul while he was visiting for the Pulse of Asia 2013 in Seoul. In this interview, Dr. Lakatta explains and describes vascular aging and aging.

  8. [Dr. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements. (Part 7: The academic carrier of Dr. Michiharu Matsuoka--from elementary school to the graduate school, Imperial University of Tokyo)].

    PubMed

    Hirotani, Hayato

    2011-12-01

    The background of the higher education of Dr. Michiharu Matsuoka shown on the official resume was disclosed by Dr. Kazuo Naito in 1986, but the courses of the elementary and secondary schools were not described in it. In regard to his lower educational courses, the author referred to the laws and regulations issued by the Ministry of Education of the Japan Government and the Yamaguchi Prefectural Office. Those were often revised with times. The author presumed the elementary school (Murozumi Primary School [the first established primary school at the birthplace; Murozumi, Hikari-City, Yamaguchi Prefecture]) and middle schools (Prefectural Yamaguchi Middle School and Yamaguchi High School) to which he had been admitted. These presumptions were made to explain his whole educational course without unreasonableness. After finishing the first school year of the Yamaguchi High School, he was transferred to the Preparatory Course of the Yamaguchi Higher School (Yamaguchi Kotô Chugakkô, Yoka), because of the amendment of the educational system. Then he was transferred to the Preparatory Course of the Daisan Higher School (Daisan Kotô Chugakkô, Yoka), and to the Preparatory Course of Daiichi Higher School (Daiichi Kotô Chugakkô, Yoka). After his graduation from the Regular Course of the Daiichi Higher School (Daiichi Kotô Chugakkô, Honka), he was admitted to the Medical College of the Imperial University from which he graduated in 1897. In addition, he was a medical student of the Graduate School of the Imperial University of Tokyo just before he left Japan for studying abroad. The whole academic carrier of Dr. Matsuoka is not only clearly clarified, but it is also indicated that he was one of the successful examples of the educational system proposed by Yamaguchi Prefecture in Meiji era which articulated the local primary and middle schools with the Imperial University of Tokyo. PMID:22586890

  9. [Dr. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements (Part 6: Studying abroad of Dr. Matsuoka and opening to public, reputation and achievement of the department)].

    PubMed

    Hirotani, Hayato

    2011-03-01

    Dr. Michiharu Matsuoka studied orthopaedic surgery in Germany, Austria and other countries during the period from August, 1902 to May, 1906. He visited many university pathological institutes and surgical and orthopaedic clinics to study pathology and to learn the practice of orthopaedic surgery. After that, he started his practice at the newly established Department of Orthopaedic Surgery in the Medical School of Kyoto Imperial University in June, 1906. The department was opened in 1907 and in 1911 it was opened to all citizens and practical doctors in Kyoto City and exhibited many orthopaedic specimens and instruments. In particular, the x-ray apparatus of the Department was so well equipped that a German radiologist who visited the Department admired it in his article that was published in the journal of radiology in 1911. The Department was not surpassed by others for the number of patients with the dislocation of the hip and tuberculous spondylitis as well as the advanced quality and variety of roentgenological and pathological researches on these diseases. PMID:21797054

  10. [Ol'ha Petrivna Chepinoha--a founder of investigations of nucleic acids in biochemistry in Ukraine. To the 100th anniversary of birthday, 1.07.1907--27.04.1983].

    PubMed

    Vynohradova, R P

    2008-01-01

    Olga Petrivna Chepinoga, doctor of science (biology), senior scientific worker, was born on July 1, 1907, in Kyiv. She graduated from the 1st Kyiv Medical Institute (1927-1931). In 1931-1935 she worked at various medical institutions of Ukraine. In 1935 O. P. Chepinoga was employed by the Institute of Biochemistry of the National Academy of Sciences of the Ukr.SSR as a laborant, then as an assistant, junior and senior scientific worker. In 1940 O. P. Chepinoga defended a thesis for a Candidate's degree, and from 1941 she was given a rank of the senior scientific worker. During the Great Patriotic War she served in the armed forces of the Soviet Army (1941-1945) as a medical officer in the rank of captain. In 1944-1963 she worked at the Instutute of Biochemistry of the AS of the Ukr.SSR as a senior scientific worker, and in 1963-1965 headed the Laboratory of Nucleic Acids. In 1952 O. P. Chepinoga defended a thesis for Doctor's degree in biology On Biologic Role of Nucleic Acids. Investigations of O. P. Chepinoga were first devoted to oxidation processes in muscles in various physiologic conditions, physico-chemical properties of myosin and its ATPase activity. Since 1948 her scientific interests had been concentrating on studying the biologic role and metabolism of nucleic acids, their transformation in the organism in norm and in pathological states. She was the first to find that various proteins interacted with DNA molecule. The highest activity of DNAse and RNAse was revealed in the organs which permanently synthesize proteins (liver, spleen, pancreas). Under quantitative undifferentiated growth of malignant tumors (Brown-Pierse carcinoma and Crocker sarcoma) the great part belongs to the process of DNA disintegrations; DNAse activity increases considerably in the animal and human blood that is not observed at other somatic diseases and is of great diagnostic value. Considerable shifts in DNAse activity at various pathologies were not found. The enrichment of transport RNA with methyl groups with chemical modifications does not disturb the integrity of the polynucleotide chain and secondary structure but decreases their acceptor activity. O. P. Chepinoga has published 100 scientific works including one monograph and one handbook. Two candidate's theses were defended under her supervision. She was awarded the medals For Courage, For the Victory over Germany in the Great Patriotic War of 1941-1945 and numerous jubilee medals. PMID:19140460

  11. The structure of Sinorhizobium meliloti phage ΦM12, which has a novel T=19l triangulation number and is the founder of a new group of T4-superfamily phages.

    PubMed

    Stroupe, M Elizabeth; Brewer, Tess E; Sousa, Duncan R; Jones, Kathryn M

    2014-02-01

    ΦM12 is the first example of a T=19l geometry capsid, encapsulating the recently sequenced genome. Here, we present structures determined by cryo-EM of full and empty capsids. The structure reveals the pattern for assembly of 1140 HK97-like capsid proteins, pointing to interactions at the pseudo 3-fold symmetry axes that hold together the asymmetric unit. The particular smooth surface of the capsid, along with a lack of accessory coat proteins encoded by the genome, suggest that this interface is the primary mechanism for capsid assembly. Two-dimensional averages of the tail, including the neck and baseplate, reveal that ΦM12 has a relatively narrow neck that attaches the tail to the capsid, as well as a three-layer baseplate. When free from DNA, the icosahedral edges expand by about 5nm, while the vertices stay at the same position, forming a similarly smooth, but bowed, T=19l icosahedral capsid.

  12. Identification of the Interactors of Human Nibrin (NBN) and of Its 26 kDa and 70 kDa Fragments Arising from the NBN 657del5 Founder Mutation

    PubMed Central

    Pennisi, Rosa; Pallotta, Valeria; D'Alessandro, Angelo; Antoccia, Antonio; Zolla, Lello; Ascenzi, Paolo; di Masi, Alessandra

    2014-01-01

    Nibrin (also named NBN or NBS1) is a component of the MRE11/RAD50/NBN complex, which is involved in early steps of DNA double strand breaks sensing and repair. Mutations within the NBN gene are responsible for the Nijmegen breakage syndrome (NBS). The 90% of NBS patients are homozygous for the 657del5 mutation, which determines the synthesis of two truncated proteins of 26 kDa (p26) and 70 kDa (p70). Here, HEK293 cells have been exploited to transiently express either the full-length NBN protein or the p26 or p70 fragments, followed by affinity chromatography enrichment of the eluates. The application of an unsupervised proteomics approach, based upon SDS-PAGE separation and shotgun digestion of protein bands followed by MS/MS protein identification, indicates the occurrence of previously unreported protein interacting partners of the full-length NBN protein and the p26 fragment containing the FHA/BRCT1 domains, especially after cell irradiation. In particular, results obtained shed light on new possible roles of NBN and of the p26 fragment in ROS scavenging, in the DNA damage response, and in protein folding and degradation. In particular, here we show that p26 interacts with PARP1 after irradiation, and this interaction exerts an inhibitory effect on PARP1 activity as measured by NAD+ levels. Furthermore, the p26-PARP1 interaction seems to be responsible for the persistence of ROS, and in turn of DSBs, at 24 h from IR. Since some of the newly identified interactors of the p26 and p70 fragments have not been found to interact with the full-length NBN, these interactions may somehow contribute to the key biological phenomena underpinning NBS. PMID:25485873

  13. [Dr. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements (Part 6: Studying abroad of Dr. Matsuoka and opening to public, reputation and achievement of the department)].

    PubMed

    Hirotani, Hayato

    2011-03-01

    Dr. Michiharu Matsuoka studied orthopaedic surgery in Germany, Austria and other countries during the period from August, 1902 to May, 1906. He visited many university pathological institutes and surgical and orthopaedic clinics to study pathology and to learn the practice of orthopaedic surgery. After that, he started his practice at the newly established Department of Orthopaedic Surgery in the Medical School of Kyoto Imperial University in June, 1906. The department was opened in 1907 and in 1911 it was opened to all citizens and practical doctors in Kyoto City and exhibited many orthopaedic specimens and instruments. In particular, the x-ray apparatus of the Department was so well equipped that a German radiologist who visited the Department admired it in his article that was published in the journal of radiology in 1911. The Department was not surpassed by others for the number of patients with the dislocation of the hip and tuberculous spondylitis as well as the advanced quality and variety of roentgenological and pathological researches on these diseases.

  14. [Ol'ha Petrivna Chepinoha--a founder of investigations of nucleic acids in biochemistry in Ukraine. To the 100th anniversary of birthday, 1.07.1907--27.04.1983].

    PubMed

    Vynohradova, R P

    2008-01-01

    Olga Petrivna Chepinoga, doctor of science (biology), senior scientific worker, was born on July 1, 1907, in Kyiv. She graduated from the 1st Kyiv Medical Institute (1927-1931). In 1931-1935 she worked at various medical institutions of Ukraine. In 1935 O. P. Chepinoga was employed by the Institute of Biochemistry of the National Academy of Sciences of the Ukr.SSR as a laborant, then as an assistant, junior and senior scientific worker. In 1940 O. P. Chepinoga defended a thesis for a Candidate's degree, and from 1941 she was given a rank of the senior scientific worker. During the Great Patriotic War she served in the armed forces of the Soviet Army (1941-1945) as a medical officer in the rank of captain. In 1944-1963 she worked at the Instutute of Biochemistry of the AS of the Ukr.SSR as a senior scientific worker, and in 1963-1965 headed the Laboratory of Nucleic Acids. In 1952 O. P. Chepinoga defended a thesis for Doctor's degree in biology On Biologic Role of Nucleic Acids. Investigations of O. P. Chepinoga were first devoted to oxidation processes in muscles in various physiologic conditions, physico-chemical properties of myosin and its ATPase activity. Since 1948 her scientific interests had been concentrating on studying the biologic role and metabolism of nucleic acids, their transformation in the organism in norm and in pathological states. She was the first to find that various proteins interacted with DNA molecule. The highest activity of DNAse and RNAse was revealed in the organs which permanently synthesize proteins (liver, spleen, pancreas). Under quantitative undifferentiated growth of malignant tumors (Brown-Pierse carcinoma and Crocker sarcoma) the great part belongs to the process of DNA disintegrations; DNAse activity increases considerably in the animal and human blood that is not observed at other somatic diseases and is of great diagnostic value. Considerable shifts in DNAse activity at various pathologies were not found. The enrichment of transport RNA with methyl groups with chemical modifications does not disturb the integrity of the polynucleotide chain and secondary structure but decreases their acceptor activity. O. P. Chepinoga has published 100 scientific works including one monograph and one handbook. Two candidate's theses were defended under her supervision. She was awarded the medals For Courage, For the Victory over Germany in the Great Patriotic War of 1941-1945 and numerous jubilee medals.

  15. [Štampar's contemporary Josip Šilović: the founder of the Colonization fund for orphans from hunger-stricken Croatian areas and the Fund for orphans of Croatian emigrants during World War I].

    PubMed

    Szabo, Agneza

    2015-11-01

    This article gives a brief review of the scientific, academic, and political activity of Josip Šilović, and most importantly of his humanitarian work. He will be remembered for saving thousands of children who lost their fathers or brothers to World War I and who were left to starve to death. To this end Šilović and his associates established several funds and organisations, most notably Narodna zaštita. He continued with his humanitarian activities until he died in Zagreb in 1939.

  16. [Štampar's contemporary Josip Šilović: the founder of the Colonization fund for orphans from hunger-stricken Croatian areas and the Fund for orphans of Croatian emigrants during World War I].

    PubMed

    Szabo, Agneza

    2015-11-01

    This article gives a brief review of the scientific, academic, and political activity of Josip Šilović, and most importantly of his humanitarian work. He will be remembered for saving thousands of children who lost their fathers or brothers to World War I and who were left to starve to death. To this end Šilović and his associates established several funds and organisations, most notably Narodna zaštita. He continued with his humanitarian activities until he died in Zagreb in 1939. PMID:27639043

  17. Analysis of Latvian familial melanoma patients shows novel variants in the noncoding regions of CDKN2A and that the CDK4 mutation R24H is a founder mutation.

    PubMed

    Veinalde, Rūta; Ozola, Aija; Azarjana, Kristīne; Molven, Anders; Akslen, Lars A; Doniņa, Simona; Proboka, Guna; Cēma, Ingrīda; Baginskis, Ainārs; Pjanova, Dace

    2013-06-01

    Hereditary cutaneous melanoma is associated with mutations in the high-risk CDKN2A gene in about 40% of melanoma-prone families. Mutations in the CDK4 gene are the cause in only a few pedigrees. In this study, we analyzed 20 Latvian familial melanoma probands and carried out a comprehensive analysis of CDKN2A including sequencing of its promoter/intronic regions and deletion screening. We also analyzed the critical second exon of the CDK4 gene. One novel intronic variant (IVS2+82C>T) of the CDKN2A gene and a small deletion (c.-20677_-20682delGTACGC) in its promoter region were found. Genotyping of the novel variants in larger melanoma and control groups indicated that the deletion increases the risk of melanoma (odds ratio=6.353, 95% confidence interval: 1.34-30.22, P=0.0168). The CDK4 gene analysis showed a Latvian melanoma family with the mutation R24H carried on the same haplotype as in two previously described Latvian CDK4-positive families. Our study suggests that the main risk gene in Latvian families with a strong family history of melanoma is CDK4 and that most of the other cases analyzed could be sporadic or associated with low-penetrance risk genes.

  18. Metabolomic assessment of key maize resources: GC-MS and NMR profiling of grain from B73 hybrids of the nested association mapping (NAM) founders and of geographically diverse landraces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study expands metabolomic assessments of maize beyond commercial elite lines to include two sets of publicly available lines used extensively in the scientific community to investigate the genetic basis of complex plant traits or that may serve as a source of new alleles for improving mo...

  19. Analysis of Latvian familial melanoma patients shows novel variants in the noncoding regions of CDKN2A and that the CDK4 mutation R24H is a founder mutation.

    PubMed

    Veinalde, Rūta; Ozola, Aija; Azarjana, Kristīne; Molven, Anders; Akslen, Lars A; Doniņa, Simona; Proboka, Guna; Cēma, Ingrīda; Baginskis, Ainārs; Pjanova, Dace

    2013-06-01

    Hereditary cutaneous melanoma is associated with mutations in the high-risk CDKN2A gene in about 40% of melanoma-prone families. Mutations in the CDK4 gene are the cause in only a few pedigrees. In this study, we analyzed 20 Latvian familial melanoma probands and carried out a comprehensive analysis of CDKN2A including sequencing of its promoter/intronic regions and deletion screening. We also analyzed the critical second exon of the CDK4 gene. One novel intronic variant (IVS2+82C>T) of the CDKN2A gene and a small deletion (c.-20677_-20682delGTACGC) in its promoter region were found. Genotyping of the novel variants in larger melanoma and control groups indicated that the deletion increases the risk of melanoma (odds ratio=6.353, 95% confidence interval: 1.34-30.22, P=0.0168). The CDK4 gene analysis showed a Latvian melanoma family with the mutation R24H carried on the same haplotype as in two previously described Latvian CDK4-positive families. Our study suggests that the main risk gene in Latvian families with a strong family history of melanoma is CDK4 and that most of the other cases analyzed could be sporadic or associated with low-penetrance risk genes. PMID:23546221

  20. Molecular Phylogenetic Evaluation of Classification and Scenarios of Character Evolution in Calcareous Sponges (Porifera, Class Calcarea)

    PubMed Central

    Voigt, Oliver; Wülfing, Eilika; Wörheide, Gert

    2012-01-01

    Calcareous sponges (Phylum Porifera, Class Calcarea) are known to be taxonomically difficult. Previous molecular studies have revealed many discrepancies between classically recognized taxa and the observed relationships at the order, family and genus levels; these inconsistencies question underlying hypotheses regarding the evolution of certain morphological characters. Therefore, we extended the available taxa and character set by sequencing the complete small subunit (SSU) rDNA and the almost complete large subunit (LSU) rDNA of additional key species and complemented this dataset by substantially increasing the length of available LSU sequences. Phylogenetic analyses provided new hypotheses about the relationships of Calcarea and about the evolution of certain morphological characters. We tested our phylogeny against competing phylogenetic hypotheses presented by previous classification systems. Our data reject the current order-level classification by again finding non-monophyletic Leucosolenida, Clathrinida and Murrayonida. In the subclass Calcinea, we recovered a clade that includes all species with a cortex, which is largely consistent with the previously proposed order Leucettida. Other orders that had been rejected in the current system were not found, but could not be rejected in our tests either. We found several additional families and genera polyphyletic: the families Leucascidae and Leucaltidae and the genus Leucetta in Calcinea, and in Calcaronea the family Amphoriscidae and the genus Ute. Our phylogeny also provided support for the vaguely suspected close relationship of several members of Grantiidae with giantortical diactines to members of Heteropiidae. Similarly, our analyses revealed several unexpected affinities, such as a sister group relationship between Leucettusa (Leucaltidae) and Leucettidae and between Leucascandra (Jenkinidae) and Sycon carteri (Sycettidae). According to our results, the taxonomy of Calcarea is in desperate need of a

  1. Molecular phylogenetic evaluation of classification and scenarios of character evolution in calcareous sponges (Porifera, Class Calcarea).

    PubMed

    Voigt, Oliver; Wülfing, Eilika; Wörheide, Gert

    2012-01-01

    Calcareous sponges (Phylum Porifera, Class Calcarea) are known to be taxonomically difficult. Previous molecular studies have revealed many discrepancies between classically recognized taxa and the observed relationships at the order, family and genus levels; these inconsistencies question underlying hypotheses regarding the evolution of certain morphological characters. Therefore, we extended the available taxa and character set by sequencing the complete small subunit (SSU) rDNA and the almost complete large subunit (LSU) rDNA of additional key species and complemented this dataset by substantially increasing the length of available LSU sequences. Phylogenetic analyses provided new hypotheses about the relationships of Calcarea and about the evolution of certain morphological characters. We tested our phylogeny against competing phylogenetic hypotheses presented by previous classification systems. Our data reject the current order-level classification by again finding non-monophyletic Leucosolenida, Clathrinida and Murrayonida. In the subclass Calcinea, we recovered a clade that includes all species with a cortex, which is largely consistent with the previously proposed order Leucettida. Other orders that had been rejected in the current system were not found, but could not be rejected in our tests either. We found several additional families and genera polyphyletic: the families Leucascidae and Leucaltidae and the genus Leucetta in Calcinea, and in Calcaronea the family Amphoriscidae and the genus Ute. Our phylogeny also provided support for the vaguely suspected close relationship of several members of Grantiidae with giantortical diactines to members of Heteropiidae. Similarly, our analyses revealed several unexpected affinities, such as a sister group relationship between Leucettusa (Leucaltidae) and Leucettidae and between Leucascandra (Jenkinidae) and Sycon carteri (Sycettidae). According to our results, the taxonomy of Calcarea is in desperate need of a

  2. Making the Constitution. SSEC American History Series.

    ERIC Educational Resources Information Center

    Ladenburg, Thomas

    This unit for teaching U.S. history was designed to help students understand, appreciate, and analyze the magnitude of the Founders' creation. It permits them to understand issues confronting the Founders in 1787, to become involved in the process of resolving these issues, to comprehend the actual solutions developed by the Founders, and to…

  3. Characterization of Bacterial, Archaeal and Eukaryote Symbionts from Antarctic Sponges Reveals a High Diversity at a Three-Domain Level and a Particular Signature for This Ecosystem

    PubMed Central

    Rodríguez-Marconi, Susana; De la Iglesia, Rodrigo; Díez, Beatriz; Fonseca, Cássio A.; Hajdu, Eduardo; Trefault, Nicole

    2015-01-01

    Sponge-associated microbial communities include members from the three domains of life. In the case of bacteria, they are diverse, host specific and different from the surrounding seawater. However, little is known about the diversity and specificity of Eukarya and Archaea living in association with marine sponges. This knowledge gap is even greater regarding sponges from regions other than temperate and tropical environments. In Antarctica, marine sponges are abundant and important members of the benthos, structuring the Antarctic marine ecosystem. In this study, we used high throughput ribosomal gene sequencing to investigate the three-domain diversity and community composition from eight different Antarctic sponges. Taxonomic identification reveals that they belong to families Acarnidae, Chalinidae, Hymedesmiidae, Hymeniacidonidae, Leucettidae, Microcionidae, and Myxillidae. Our study indicates that there are different diversity and similarity patterns between bacterial/archaeal and eukaryote microbial symbionts from these Antarctic marine sponges, indicating inherent differences in how organisms from different domains establish symbiotic relationships. In general, when considering diversity indices and number of phyla detected, sponge-associated communities are more diverse than the planktonic communities. We conclude that three-domain microbial communities from Antarctic sponges are different from surrounding planktonic communities, expanding previous observations for Bacteria and including the Antarctic environment. Furthermore, we reveal differences in the composition of the sponge associated bacterial assemblages between Antarctic and tropical-temperate environments and the presence of a highly complex microbial eukaryote community, suggesting a particular signature for Antarctic sponges, different to that reported from other ecosystems. PMID:26421612

  4. Characterization of Bacterial, Archaeal and Eukaryote Symbionts from Antarctic Sponges Reveals a High Diversity at a Three-Domain Level and a Particular Signature for This Ecosystem.

    PubMed

    Rodríguez-Marconi, Susana; De la Iglesia, Rodrigo; Díez, Beatriz; Fonseca, Cássio A; Hajdu, Eduardo; Trefault, Nicole

    2015-01-01

    Sponge-associated microbial communities include members from the three domains of life. In the case of bacteria, they are diverse, host specific and different from the surrounding seawater. However, little is known about the diversity and specificity of Eukarya and Archaea living in association with marine sponges. This knowledge gap is even greater regarding sponges from regions other than temperate and tropical environments. In Antarctica, marine sponges are abundant and important members of the benthos, structuring the Antarctic marine ecosystem. In this study, we used high throughput ribosomal gene sequencing to investigate the three-domain diversity and community composition from eight different Antarctic sponges. Taxonomic identification reveals that they belong to families Acarnidae, Chalinidae, Hymedesmiidae, Hymeniacidonidae, Leucettidae, Microcionidae, and Myxillidae. Our study indicates that there are different diversity and similarity patterns between bacterial/archaeal and eukaryote microbial symbionts from these Antarctic marine sponges, indicating inherent differences in how organisms from different domains establish symbiotic relationships. In general, when considering diversity indices and number of phyla detected, sponge-associated communities are more diverse than the planktonic communities. We conclude that three-domain microbial communities from Antarctic sponges are different from surrounding planktonic communities, expanding previous observations for Bacteria and including the Antarctic environment. Furthermore, we reveal differences in the composition of the sponge associated bacterial assemblages between Antarctic and tropical-temperate environments and the presence of a highly complex microbial eukaryote community, suggesting a particular signature for Antarctic sponges, different to that reported from other ecosystems.

  5. The fatty acids of calcareous sponges (Calcarea, Porifera).

    PubMed

    Schreiber, Andrea; Wörheide, Gert; Thiel, Volker

    2006-09-01

    Twenty-nine specimens of calcareous sponges (Class Calcarea, Phylum Porifera), covering thirteen representative species of the families Soleneiscidae, Leucaltidae, Levinellidae, Leucettidae, Clathrinidae, Sycettidae, Grantiidae, Jenkinidae, and Heteropiidae were analysed for their fatty acids. The fatty acids of Calcarea generally comprise saturated and monounsaturated linear (n-), and terminally methylated (iso-, anteiso-) C(14)-C(20) homologues. Furthermore, polyunsaturated C(22) fatty acids and the isoprenoic 4,8,12-trimethyltridecanoic acid were found. The most prominent compounds are n-C(16), iso-C(17), iso-C(18), n-C(18), n-C(20). In addition, a high abundance of the exotic 16-methyloctadecanoic acid (anteiso-C(19)) appears to be a characteristic trait of Calcarea. Long-chain 'demospongic acids', typically found in Demospongiae and Hexactinellida, are absent in Calcarea. The completely different strategy of calcarean fatty acid synthesis supports their phylogenetic distinctiveness from a common Demospongiae/Hexactinellida taxon. Both intraspecific and intraclass patterns of Calcarea showed great similarity, suggesting a conserved fatty acid composition that already existed in the last common ancestor of Calcinea and Calcaronea, i.e. before subclasses diverged.

  6. Characterization of Bacterial, Archaeal and Eukaryote Symbionts from Antarctic Sponges Reveals a High Diversity at a Three-Domain Level and a Particular Signature for This Ecosystem.

    PubMed

    Rodríguez-Marconi, Susana; De la Iglesia, Rodrigo; Díez, Beatriz; Fonseca, Cássio A; Hajdu, Eduardo; Trefault, Nicole

    2015-01-01

    Sponge-associated microbial communities include members from the three domains of life. In the case of bacteria, they are diverse, host specific and different from the surrounding seawater. However, little is known about the diversity and specificity of Eukarya and Archaea living in association with marine sponges. This knowledge gap is even greater regarding sponges from regions other than temperate and tropical environments. In Antarctica, marine sponges are abundant and important members of the benthos, structuring the Antarctic marine ecosystem. In this study, we used high throughput ribosomal gene sequencing to investigate the three-domain diversity and community composition from eight different Antarctic sponges. Taxonomic identification reveals that they belong to families Acarnidae, Chalinidae, Hymedesmiidae, Hymeniacidonidae, Leucettidae, Microcionidae, and Myxillidae. Our study indicates that there are different diversity and similarity patterns between bacterial/archaeal and eukaryote microbial symbionts from these Antarctic marine sponges, indicating inherent differences in how organisms from different domains establish symbiotic relationships. In general, when considering diversity indices and number of phyla detected, sponge-associated communities are more diverse than the planktonic communities. We conclude that three-domain microbial communities from Antarctic sponges are different from surrounding planktonic communities, expanding previous observations for Bacteria and including the Antarctic environment. Furthermore, we reveal differences in the composition of the sponge associated bacterial assemblages between Antarctic and tropical-temperate environments and the presence of a highly complex microbial eukaryote community, suggesting a particular signature for Antarctic sponges, different to that reported from other ecosystems. PMID:26421612

  7. Glasser's Choice Theory and Purkey's Invitational Education--Allied Approaches to Counseling and Schooling

    ERIC Educational Resources Information Center

    Zeeman, Roger D.

    2006-01-01

    This article presents and compares the similar views of William Glasser, M.D., founder and president of the William Glasser Institute in Los Angeles, and author of scores of best selling books; and William Watson Purkey, Ed.D, co-founder of the International Association for Invitational Education (IAIE), Professor Emeritus at the University of…

  8. Perils of Accommodation: The Case of Joseph W. Holley

    ERIC Educational Resources Information Center

    O'Brien, Thomas V.

    2007-01-01

    This study examines accommodationism, a tactic of racial uplift used by black school founders and teachers in the Jim Crow South. For founders, accommodationism was a dangerous process of collaboration, resistance, and compromise. The subject under study is Joseph Winthrop Holley. Born in South Carolina, Holley studied in the North at Phillips…

  9. The Triumph of Religious Education for Citizenship in English Schools, 1935-1949

    ERIC Educational Resources Information Center

    Freathy, Rob

    2008-01-01

    The failure of the Association for Education in Citizenship to gain official support for the secular and pedagogically progressive forms of education for citizenship that its founder members endorsed has previously been explained by the political impotence of the association's founder members and the professional conservatism of the educational…

  10. Unity vs. Uniformity: The Influence of Ziya Gökalp and John Dewey on the Education System of the Republic of Turkey

    ERIC Educational Resources Information Center

    Celik, Rasit

    2014-01-01

    Creating a democratic nation-state and sustaining its progress was seen by the founders of the Republic of Turkey as necessary to achieving the goal of becoming a distinguished member among developed civilizations. The founders conceived of education as a main instrument in disseminating this new ideology and ensuring the emergence of a culture of…

  11. Imaging Acute Neuromuscular Explants from Thy1 Mouse Lines.

    PubMed

    Marinković, Petar; Godinho, Leanne; Misgeld, Thomas

    2015-09-01

    Because core facilities that generate transgenic founder mice for a reasonable fee are now available at most major research institutions, generating new Thy1-XFP transgenic animals (in which XFP stands for any fluorescent protein) is an option even for relatively small laboratories. Here, we provide a protocol for screening offspring of Thy1 transgenic founders. Acute neuromuscular explants are obtained from 3-wk-old F1 mice that have been produced by crossing Thy1 transgenic founders and commercially obtained inbred mice. Thy1-driven expression is detected by fluorescence microscopy. PMID:26330628

  12. The Italian neurological schools of the twentieth century

    PubMed Central

    Bonavita, Vincenzo

    Summary This lecture is not a historical lecture, but rather a journey through the “story” of neurology in Italy from its “prehistoric” beginning in the 19th century. The birth of a neurological school is that magical moment in which a founder attracts disciples: the more capable this founder is of transmitting methodology and allowing his pupils intellectual freedom, the longer his memory will live on. On the basis of this idea, the scientific biography of a few leading Italian neurologists of the 20th century is outlined, starting from Leonardo Bianchi, founder of the Italian Neurological Society in 1907. PMID:21729589

  13. Old Dad Chiro: his thoughts, words, and deeds

    PubMed Central

    Brown, Myron D.

    2010-01-01

    Objective This article offers the author's opinions about some of the thoughts, words, and deeds of the profession's founder, Daniel David Palmer. Discussion Reviewing D.D. Palmer's writings is challenging because he was the discoverer and founder of a developing profession and therefore his thoughts and words were rapidly evolving. Statements made by Palmer without judicious consideration of context could easily be misunderstood. Conclusion D.D. Palmer was individualistic and enigmatic. This commentary provides a look at the whole in an attempt to reveal the character and spirit of the founder. PMID:22693470

  14. John Whitridge Williams, MD (1866–1931) of Baltimore: pioneer of academic obstetrics

    PubMed Central

    Dunn, P M

    2007-01-01

    Williams was the founder of academic obstetrics in the United States and with his textbook was the recognised leader of this discipline in America during the first 30 years of the 20th century. PMID:17185435

  15. From Baptist to Catholic.

    ERIC Educational Resources Information Center

    Easterbrook, Michael

    2002-01-01

    Describes how the small Ave Maria College of the Americas in Nicaragua, which turned from Baptist to Roman Catholic after receiving $3 million from the founder of Domino's, has had a difficult transition. (EV)

  16. 76 FR 44574 - Yavapai County Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-26

    ...; 9 a.m to 2 p.m. ADDRESSES: The meeting will be held at the Prescott Public Library, Founders Suite A....us . SUPPLEMENTARY INFORMATION: The meeting is open to the public. The following business will...

  17. Q&A with Tom Snyder

    ERIC Educational Resources Information Center

    McLester, Susan

    2005-01-01

    In this article, an interview with Tom Snyder, founder of Tom Snyder Productions in 1980, is presented. One of the topics discussed here is Snyder's biggest turning point in education technology over the past 25 years.

  18. Obituary: John Louis Perdrix (1926-2005)

    NASA Astrophysics Data System (ADS)

    Orchiston, W.

    2005-12-01

    On 27 June 2005 the Journal of Astronomical History and Heritage lost its founder and Australia lost one of its leading historians of astronomy when John Louis Perdrix died in Dubai after a brief battle with cancer.

  19. Pioneer Profile.

    ERIC Educational Resources Information Center

    Butcher, Channa Beth

    1987-01-01

    Profiles Herbert A. Sweet, founder and director of Acorn Farms Day Camp (Indiana) for 44 years. Includes reminiscences about the camp's program, staffing, food, World War II, affiliation with the American Camping Association, and camps/directors of today. (NEC)

  20. Alternative Treatments for Ankylosing Spondylitis

    MedlinePlus

    ... eNewsletter Planned Giving Quest Legacy Society Donate Your Vehicle Volunteer Fundraising Contact Us About The Founder - Jane ... free AS brochure , geared specifically to chiropractors! Chiropractic Management of Low Back Disorders: Report From a Consensus ...

  1. Multiple Myeloma Research Foundation

    MedlinePlus

    ... MMRF Founder honored by PharmaVOICE magazine for continued innovation and improving patient outcomes Read More June 3, ... Dr. Nancy Snyderman at the 2016 World Medical Innovation Forum Watch Now April 27, 2016 "These 3 ...

  2. Space Flute Duet

    NASA Video Gallery

    Harmony reaches new heights as NASA Astronaut Cady Coleman, circling Earth aboard the International Space Station, and musician Ian Anderson, founder of the rock band Jethro Tull, join together for...

  3. Extrapolate the Past... or Invent the Future

    ScienceCinema

    Vinod Khosla

    2016-07-12

    Berkeley Lab's Environmental Energy Technologies Division launches its Distinguished Lecturer series with a talk by Vinod Khosla, founder of Khosla Ventures, whose mission is to "assist great entre...  

  4. 3 CFR 8457 - Proclamation 8457 of November 20, 2009. National Child's Day, 2009

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... founders to give all our children a fair chance and an equal start in life. NOW, THEREFORE, I, BARACK OBAMA... nine, and of the Independence of the United States of America the two hundred and thirty-fourth.BARACK OBAMA...

  5. Association between familial hypercholesterolaemia and church affiliation. Is this the result of sociocultural isolation of migrant farmers in 19th-century South Africa?

    PubMed

    Torrington, M; Botha, J L; Pilcher, G J; Baker, S G

    1984-05-12

    The family trees of 57 Afrikaans -speaking familial hypercholesterolaemia (FH) index cases were traced to look for founder surnames, for an association between FH and affiliation to the Gereformeerde Kerk (GK), and for consanguinity. Two possible founder surnames were identified. Each occurred in more than 5% of individuals and both were well known among the founders of the GK. Affiliation to the GK was much more common in our sample (45% of 994 individuals) than in the general population (5%), an overall odds ratio of 7,38. This association was stronger in older generations. There were 21 consanguineous marriages, the two suspected founder surnames and affiliation to the GK featuring prominently among them. PMID:6719310

  6. Q & A with Ed Tech Leaders: Interview with Clark Aldrich

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.; Fulgham, Susan M.

    2016-01-01

    Clark Aldrich is the founder and Managing Partner of Clark Aldrich Designs, and is known as a global education visionary, industry analyst, and speaker. In this interview, he responds to questions about his ideas, his work, and his theories.

  7. John Dewey--Philosopher and Educational Reformer

    ERIC Educational Resources Information Center

    Talebi, Kandan

    2015-01-01

    John Dewey was an American philosopher and educator, founder of the philosophical movement known as pragmatism, a pioneer in functional psychology, and a leader of the progressive movement in education in the United States.

  8. A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages

    PubMed Central

    Costa, Marta D.; Pereira, Joana B.; Pala, Maria; Fernandes, Verónica; Olivieri, Anna; Achilli, Alessandro; Perego, Ugo A.; Rychkov, Sergei; Naumova, Oksana; Hatina, Jiři; Woodward, Scott R.; Eng, Ken Khong; Macaulay, Vincent; Carr, Martin; Soares, Pedro; Pereira, Luísa; Richards, Martin B.

    2013-01-01

    The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we show that all four major founders, ~40% of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than the Near East or Caucasus. Furthermore, most of the remaining minor founders share a similar deep European ancestry. Thus the great majority of Ashkenazi maternal lineages were not brought from the Levant, as commonly supposed, nor recruited in the Caucasus, as sometimes suggested, but assimilated within Europe. These results point to a significant role for the conversion of women in the formation of Ashkenazi communities, and provide the foundation for a detailed reconstruction of Ashkenazi genealogical history. PMID:24104924

  9. Simulating Genetic Change in a Large Lecture Hall: The Ultimate Bean Counting Experience.

    ERIC Educational Resources Information Center

    Brewer, Carol A.; Zabinski, Catherine

    1999-01-01

    Describes a simulation exercise designed to illustrate the influence of founder effects, genetic drift, and gene flow. Also presents strategies for using cooperative learning in large lecture settings. (WRM)

  10. E. L. Godkin and the Science of Society.

    ERIC Educational Resources Information Center

    Caudill, Edward

    1989-01-01

    Studies the tenure of Edwin Lawrence Godkin, founder of "The Nation" magazine. Examines Godkin's ideas about social science, and explores the relationship of his ideas to nineteenth-century concepts of natural law. (MM)

  11. Extrapolate the Past... or Invent the Future

    SciTech Connect

    Vinod Khosla

    2008-10-14

    Berkeley Lab's Environmental Energy Technologies Division launches its Distinguished Lecturer series with a talk by Vinod Khosla, founder of Khosla Ventures, whose mission is to "assist great entre...  

  12. [Evgeniĭ Ventseslavovich Pelikan. On the occasion of the 150th anniversary of the journal "Arkhiv sudebnoy meditsiny and obshchestvennoy gigieny (Archive of forensic medicine and public hygiene)"].

    PubMed

    Nazarov, V Yu

    2015-01-01

    This article is devoted to the life and multi-faceted activities of Evgeniy Ventseslavovich Pelikan, a physician, administrator, and the founder of the first Russian journal of forensic medicine. PMID:25874323

  13. Charcot's son, commander Jean-Baptiste Charcot: from neurology to "Pourquoi Pas?".

    PubMed

    Teive, Hélio A G; Munhoz, Renato P; Simões, Jefferson C

    2012-04-01

    Charcot name became very famous around the world, firstly because of the work of Professor Jean-Martin Charcot, the founder of Clinical Neurology, and, secondly, because of his son, Jean-Baptiste, the world famous maritime explorer.

  14. ERNST WYNDER: A REMEMBRANCE

    PubMed Central

    Stellman, Steven D.

    2006-01-01

    Ernst Wynder, founder and President of the American Health Foundation, was my employer, mentor, and colleague for nearly 25 years. This brief rememberance provides some experiences and perspectives that influenced my career as a cancer epidemiologist. PMID:16999987

  15. Inside Beacon Hill: Bertrand Russell as Schoolmaster.

    ERIC Educational Resources Information Center

    Jespersen, Shirley

    1987-01-01

    The author describes the life and theories of Bertrand Russell, founder of Beacon Hill School. Russell's educational theories centered on the personal autonomy of the student and democratization of the learning process. (CH)

  16. Scott Tannenbaum on the “Science of Teamwork”: HHP Directorate Innovation Lecture Series

    NASA Video Gallery

    Scott Tannenbaum, Ph.D. is President and Co-Founder of gOE. Under his leadership, gOE has served more than 500 organizations globally across all major industries. Dr. Tannenbaum is a leading expert...

  17. Chemotherapy

    MedlinePlus

    ... Brain Tumor Treatment Locations Treatment Side Effects & their Management Support and Resources Caregiver Resource Center Pediatric Caregiver Resource Center About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information ...

  18. Stereotactic Radiosurgery

    MedlinePlus

    ... Clinical Trials Alternative Medicine Treatment Side Effects & their Management Support and Resources Caregiver Resource Center About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information ...

  19. Continuum of Care

    MedlinePlus

    ... Brain Tumor Treatment Locations Treatment Side Effects & their Management Support and Resources Caregiver Resource Center Pediatric Caregiver Resource Center About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information ...

  20. Alternative and Integrative Medicine

    MedlinePlus

    ... Brain Tumor Treatment Locations Treatment Side Effects & their Management Support and Resources Caregiver Resource Center Pediatric Caregiver Resource Center About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information ...

  1. The stem cell concept in plants: a matter of debate.

    PubMed

    Laux, Thomas

    2003-05-01

    Throughout their life, which can last for over a thousand years, plants have the fascinating ability to give rise to new organs from founder cells in their apical meristems. Whether these founder cells are equivalent to the pluripotent stem cells in animals has been a long-standing controversy amongst plant scientists. Here, this controversy will be addressed in light of classical observations and recent findings. PMID:12732137

  2. Genealogical analysis of maternal and paternal lineages in the Quebec population.

    PubMed

    Tremblay, Marc; Vézina, Hélène

    2010-04-01

    The Quebec population is one of the rare populations of its size for which genealogical information is available for an uninterrupted period of almost four centuries. This allows for in-depth studies on the formation and evolution of a young founder population. Using data from two major population registers, in this study we focus on the maternal and paternal lineages (i.e., strictly female or male genealogical lines) that can be traced back within the Quebec genealogies. Through the analysis of these lineages it is possible to characterize the founders who transmitted to the contemporary population their mitochondrial (for females) and Y-chromosome (for males) DNA. The basic material consists of 2,221 ascending genealogies of subjects who married in the Quebec population between 1945 and 1965. On average, more than nine generations of ancestors were identified among the lineages. Analyses of maternal and paternal lineages show that the number of paternal founders is higher and their origins and genetic contributions are more variable than that of maternal founders, leading to a larger effective population size and greater diversity of Y chromosomes than of mtDNA. This is explained for the most part by differential migratory patterns among male and female founders of the Quebec population. Comparisons of sex-specific genetic contributions with total genetic contribution showed a strong correlation between the two values, with some discrepancies related to sex ratio differences among the founders' first descendants.

  3. Mixed model approaches for the identification of QTLs within a maize hybrid breeding program.

    PubMed

    van Eeuwijk, Fred A; Boer, Martin; Totir, L Radu; Bink, Marco; Wright, Deanne; Winkler, Christopher R; Podlich, Dean; Boldman, Keith; Baumgarten, Andy; Smalley, Matt; Arbelbide, Martin; ter Braak, Cajo J F; Cooper, Mark

    2010-01-01

    Two outlines for mixed model based approaches to quantitative trait locus (QTL) mapping in existing maize hybrid selection programs are presented: a restricted maximum likelihood (REML) and a Bayesian Markov Chain Monte Carlo (MCMC) approach. The methods use the in-silico-mapping procedure developed by Parisseaux and Bernardo (2004) as a starting point. The original single-point approach is extended to a multi-point approach that facilitates interval mapping procedures. For computational and conceptual reasons, we partition the full set of relationships from founders to parents of hybrids into two types of relations by defining so-called intermediate founders. QTL effects are defined in terms of those intermediate founders. Marker based identity by descent relationships between intermediate founders define structuring matrices for the QTL effects that change along the genome. The dimension of the vector of QTL effects is reduced by the fact that there are fewer intermediate founders than parents. Furthermore, additional reduction in the number of QTL effects follows from the identification of founder groups by various algorithms. As a result, we obtain a powerful mixed model based statistical framework to identify QTLs in genetic backgrounds relevant to the elite germplasm of a commercial breeding program. The identification of such QTLs will provide the foundation for effective marker assisted and genome wide selection strategies. Analyses of an example data set show that QTLs are primarily identified in different heterotic groups and point to complementation of additive QTL effects as an important factor in hybrid performance.

  4. Historical Invasion Records Can Be Misleading: Genetic Evidence for Multiple Introductions of Invasive Raccoons (Procyon lotor) in Germany

    PubMed Central

    Fischer, Mari L.; Hochkirch, Axel; Heddergott, Mike; Schulze, Christoph; Anheyer-Behmenburg, Helena E.; Lang, Johannes; Michler, Frank-Uwe; Hohmann, Ulf; Ansorge, Hermann; Hoffmann, Lothar; Klein, Roland; Frantz, Alain C.

    2015-01-01

    Biological invasions provide excellent study systems to understand evolutionary, genetic and ecological processes during range expansions. There is strong evidence for positive effects of high propagule pressure and the associated higher genetic diversity on invasion success, but some species have become invasive despite small founder numbers. The raccoon (Procyon lotor) is often considered as a typical example for such a successful invasion resulting from a small number of founders. The species’ largest non-native population in Germany is commonly assumed to stem from a small number of founders and two separate founding events in the 1930s and 1940s. In the present study we analyzed 407 raccoons at 20 microsatellite loci sampled from the invasive range in Western Europe to test if these assumptions are correct. Contrary to the expectations, different genetic clustering methods detected evidence for at least four independent introduction events that gave rise to genetically differentiated subpopulations. Further smaller clusters were either artifacts or resulted from founder events at the range margin and recent release of captive individuals. We also found genetic evidence for on-going introductions of individuals. Furthermore a novel randomization process was used to determine the potential range of founder population size that would suffice to capture all the alleles present in a cluster. Our results falsify the assumption that this species has become widespread and abundant despite being genetically depauperate and show that historical records of species introductions may be misleading. PMID:25946257

  5. Deconstructing Jaco: genetic heritage of an Afrikaner.

    PubMed

    Greeff, J M

    2007-09-01

    It is often assumed that Afrikaners stem from a small number of Dutch immigrants. As a result they should be genetically homogeneous, show founder effects and be rather inbred. By disentangling my own South African pedigree, that is on average 12 generations deep, I try to quantify the genetic heritage of an Afrikaner. As much as 6% of my genes have been contributed by slaves from Africa, Madagascar and India, and a woman from China. This figure compares well to other genetic and genealogical estimates. Seventy three percent of my lineages coalesce into common founders, and I am related in excess of 10 times to 20 founder ancestors (30 times to Willem Schalk van der Merwe). Significant founder effects are thus possible. The overrepresentation of certain founder ancestors is in part explained by the fact that they had more children. This is remarkable given that they lived more than 300 years (or 12 generations) ago. DECONSTRUCT, a new program for pedigree analysis, identified 125 common ancestors in my pedigree. However, these common ancestors are so distant from myself, paths of between 16 and 25 steps in length, that my inbreeding coefficient is not unusually high (f approximately 0.0019).

  6. Expression of SV40 T antigen under control of rabbit uteroglobin promoter in transgenic mice.

    PubMed

    DeMayo, F J; Finegold, M J; Hansen, T N; Stanley, L A; Smith, B; Bullock, D W

    1991-08-01

    The rabbit uteroglobin gene is expressed in the lungs and reproductive tracts of male and female rabbits. To examine whether the promoter region of the uteroglobin gene could be used to target a heterologous gene to the lungs of transgenic mice, a fusion gene consisting of 3.3 kb of the 5'-flanking region of the rabbit uteroglobin gene and the large T antigen gene of the SV40 virus was constructed and microinjected into the pronuclei of one-cell mouse embryos. Eleven founder transgenic mice (5 female and 6 male) were generated. Seven of these mice developed bronchioalveolar neoplasms. Four of the founder males also developed primitive undifferentiated urogenital tract tumors. One founder female and one female offspring of a founder male developed glandular paraovarian tumors. Northern analysis revealed that the predominant site of expression of the transgene was the lung. Immunohistochemical staining showed T antigen predominantly in epithelial cells lining the bronchioles, the submucosal glands of the trachea, and the neoplasms. There appeared to be a high level of mosaicism for the transgene in the founder mice, with poor transmission of the transgene to subsequent generations. This suggests that, under the control of the uteroglobin promoter, the T antigen gene may be lethal to the fetus.

  7. Rates of inbreeding and genetic diversity in Iranian Holstein cattle.

    PubMed

    Dadar, Mohsen; Mahyari, Saeid Ansari; Rokouei, Mohammad; Edriss, Mohammd Ali

    2014-10-01

    The accumulation of inbreeding and the loss of genetic diversity is a potential problem in Holstein dairy cattle. The goal of this study was to estimate inbreeding levels and other measures of genetic diversity, using pedigree information from Iranian Holstein cattle. Edited pedigree included 1,048,572 animals. The average number of discrete generation equivalents and pedigree completeness index reached 13.4 and 90%, respectively. The rate of inbreeding was 0.3% per year. Effective number of founders, founder genomes, non-founders and ancestors of animals born between 2003 and 2011 were 503, 15.6, 16.1 and 25.7, respectively. It was proven that the unequal founder contributions as well as bottlenecks and genetic drift were important reasons for the loss of genetic diversity in the population. The top 10 ancestors with the highest marginal genetic contributions to animals born between 2003 and 2011 and with the highest contributions to inbreeding were 48.20% and 63.94%, respectively. Analyses revealed that the most important cause of genetic diversity loss was genetic drift accumulated over non-founder generations, which occurred due to small effective population size. Therefore, it seems that managing selection and mating decisions are controlling future co-ancestry and inbreeding, which would lead to better handling of the effective population size. PMID:25041055

  8. Historical Invasion Records Can Be Misleading: Genetic Evidence for Multiple Introductions of Invasive Raccoons (Procyon lotor) in Germany.

    PubMed

    Fischer, Mari L; Hochkirch, Axel; Heddergott, Mike; Schulze, Christoph; Anheyer-Behmenburg, Helena E; Lang, Johannes; Michler, Frank-Uwe; Hohmann, Ulf; Ansorge, Hermann; Hoffmann, Lothar; Klein, Roland; Frantz, Alain C

    2015-01-01

    Biological invasions provide excellent study systems to understand evolutionary, genetic and ecological processes during range expansions. There is strong evidence for positive effects of high propagule pressure and the associated higher genetic diversity on invasion success, but some species have become invasive despite small founder numbers. The raccoon (Procyon lotor) is often considered as a typical example for such a successful invasion resulting from a small number of founders. The species' largest non-native population in Germany is commonly assumed to stem from a small number of founders and two separate founding events in the 1930s and 1940s. In the present study we analyzed 407 raccoons at 20 microsatellite loci sampled from the invasive range in Western Europe to test if these assumptions are correct. Contrary to the expectations, different genetic clustering methods detected evidence for at least four independent introduction events that gave rise to genetically differentiated subpopulations. Further smaller clusters were either artifacts or resulted from founder events at the range margin and recent release of captive individuals. We also found genetic evidence for on-going introductions of individuals. Furthermore a novel randomization process was used to determine the potential range of founder population size that would suffice to capture all the alleles present in a cluster. Our results falsify the assumption that this species has become widespread and abundant despite being genetically depauperate and show that historical records of species introductions may be misleading.

  9. Exploring alternative models for sex-linked quantitative trait loci in outbred populations: application to an iberian x landrace pig intercross.

    PubMed Central

    Pérez-Enciso, Miguel; Clop, Alex; Folch, Josep M; Sánchez, Armand; Oliver, Maria A; Ovilo, Cristina; Barragán, C; Varona, Luis; Noguera, José L

    2002-01-01

    We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between outbred lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. We illustrate the method with data from an F(2) cross between Iberian x Landrace pigs for intramuscular fat content and meat color component a*. The Iberian allele exhibited a strong overdominant effect for intramuscular fat in females. There was also limited evidence of one or more regions affecting color component a*. The analysis suggested that the QTL alleles were fixed in the Iberian founders, whereas there was some evidence of segregation in Landrace for the QTL affecting a* color component. PMID:12196405

  10. Two cases of pseudologia phantastica: consideration from the viewpoint of forensic psychiatry.

    PubMed

    Akimoto, H

    1997-08-01

    Two male cases of pseudologia phantastica are reported. The first case regards unprecedented, indiscriminate murders by the use of the poison gas, sarin, and other unreasonable, almost unthinkable crimes allegedly committed by the religious cult Aum Shinrikyo, currently being examined in a criminal trial. On the basis of scrutiny of the publications of the founder of Aum Shinrikyo and his followers, as well as the founder's comments and his attitude in the courts, the author concludes that the founder of Aum is a typical pseudologia phantastica. Case 2 concerns the self-styled Professor Tsuchiya who was apparently a swindler. At least three significant deceptions have been confirmed. The forensic implications of pseudologia phantastica are discussed, as is the necessity of psychiatric evidence to assist with smooth trial proceedings. The author stresses the importance of psychiatry in preventing crimes committed by persons with pseudologia phantastica.

  11. B. F. Skinner's contributions to applied behavior analysis

    PubMed Central

    Morris, Edward K.; Smith, Nathaniel G.; Altus, Deborah E.

    2005-01-01

    Our paper reviews and analyzes B. F. Skinner's contributions to applied behavior analysis in order to assess his role as the field's originator and founder. We found, first, that his contributions fall into five categorizes: the style and content of his science, his interpretations of typical and atypical human behavior, the implications he drew from his science for application, his descriptions of possible applications, and his own applications to nonhuman and human behavior. Second, we found that he explicitly or implicitly addressed all seven dimensions of applied behavior analysis. These contributions and the dimensions notwithstanding, he neither incorporated the field's scientific (e.g., analytic) and social dimensions (e.g., applied) into any program of published research such that he was its originator, nor did he systematically integrate, advance, and promote the dimensions so to have been its founder. As the founder of behavior analysis, however, he was the father of applied behavior analysis. PMID:22478444

  12. Naturalization of plant populations: the role of cultivation and population size and density.

    PubMed

    Minton, Mark S; Mack, Richard N

    2010-10-01

    Field experimentation is required to assess the effects of environmental stochasticity on small immigrant plant populations-a widely understood but largely unexplored aspect of predicting any species' likelihood of naturalization and potential invasion. Cultivation can mitigate this stochasticity, although the outcome for a population under cultivation nevertheless varies enormously from extinction to persistence. Using factorial experiments, we investigated the effects of population size, density, and cultivation (irrigation) on the fate of founder populations for four alien species with different life history characteristics (Echinochloa frumentacea, Fagopyrum esculentum, Helianthus annuus, and Trifolium incarnatum) in eastern Washington, USA. The fate of founder populations was highly variable within and among the 3 years of experimentation and illustrates the often precarious environment encountered by plant immigrants. Larger founder populations produced more seeds (P < 0.001); the role of founder population size, however, differed among years. Irrigation resulted in higher percent survival (P < 0.001) and correspondingly larger net reproductive rate (R(0); P < 0.001). But the minimum level of irrigation for establishment, R(0) > 1, differed among years and species. Sowing density did not affect the likelihood of establishment for any species. Our results underscore the importance of environmental stochasticity in determining the fate of founder populations and the potential of cultivation and large population size in countering the long odds against naturalization. Any implementation of often proposed post-immigration field trials to assess the risk of an alien species becoming naturalized, a requisite step toward invasion, will need to assess different sizes of founder populations and the extent and character of cultivation (intentional or unintentional) that the immigrants might receive.

  13. Generation of Tissue Sections for Screening Thy1 Mouse Lines.

    PubMed

    Marinković, Petar; Godinho, Leanne; Misgeld, Thomas

    2015-09-01

    New generations of Thy1-XFP transgenic mice (where XFP stands for any fluorescent protein) can now be readily generated, given the availability of core facilities or commercial providers of Thy1 pronuclear injections. Here, we provide a protocol for screening founder progeny. Transcardial perfusion is performed on 3-wk-old F1 mice that have been produced by crossing Thy1 transgenic founders and commercially obtained inbred mice. Cryosections are generated, and Thy1-driven expression is detected by histological characterization. PMID:26330627

  14. Tensile Fabrics Enhance Architecture Around the World

    NASA Technical Reports Server (NTRS)

    2009-01-01

    Using a remarkable fabric originally developed to protect Apollo astronauts, Birdair Inc. of Amherst, New York, has crafted highly durable, safe, environmentally friendly, and architecturally stunning tensile membrane roofs for over 900 landmark structures around the world. Travelers in airports, sports fans at stadiums, and shoppers in malls have all experienced the benefits of the Teflon-coated fiberglass fabric that has enabled Birdair to grow from a small company established in its founder?s kitchen in 1955 to a multimillion-dollar specialty contractor today.

  15. Genetic analysis of captive proboscis monkeys.

    PubMed

    Ogata, Mitsuaki; Seino, Satoru

    2015-01-01

    Information on the genetic relationships of captive founders is important for captive population management. In this study, we investigated DNA polymorphisms of four microsatellite loci and the mitochondrial control region sequence of five proboscis monkeys residing in a Japanese zoo as captive founders, to clarify their genetic relationship. We found that two of the five monkeys appeared to be genetically related. Furthermore, the haplotypes of the mitochondrial control region of the five monkeys were well differentiated from the haplotypes previously reported from wild populations from the northern area of Borneo, indicating a greater amount of genetic diversity in proboscis monkeys than previously reported. PMID:25266590

  16. Robert Owen in the history of the social sciences: three presentist views.

    PubMed

    Pūras, Adomas

    2014-01-01

    This paper argues that the present-day disagreements over the right course for sociology and its public role are reflected and paralleled in contemporary historiography of Robert Owen, British social reformer and a self-described social scientist. Historical accounts, written from the perspectives of public sociology, "pure science" sociology, and anti-Marxism, interpret Owen's historical role in mutually antithetical and self-serving ways. Contrasting the three presentist accounts, I engage in an analysis of "techniques of presentism"-history-structuring concepts, such as "disciplinary founder" and "disciplinary prehistory," that allow presentist authors to get their effects. Along the way, I elaborate Peter Baehr's classification of sociology's founders. PMID:24272873

  17. Low Genetic and Morphometric Intraspecific Divergence in Peripheral Copadichromis Populations (Perciformes: Cichlidae) in the Lake Malawi Basin

    PubMed Central

    Anseeuw, Dieter; Raeymaekers, Joost A. M.; Busselen, Paul; Verheyen, Erik; Snoeks, Jos

    2011-01-01

    Peripheral isolated populations may undergo rapid divergence from the main population due to various factors such as a bottleneck or a founder effect followed by genetic drift or local selection pressures. Recent populations of two economically important Copadichromis species in Lake Malombe, a satellite lake of Lake Malawi, were neither genetically nor morphometrically distinct from their source populations in the main lake. Evidence was found for a founder effect which had a different impact on the genetic composition of the two species. In addition, the increased fishing pressure in Lake Malombe may have led to a reduction of the body sizes of both species. PMID:21716858

  18. Origins and canons: medicine and the history of sociology.

    PubMed

    Collyer, Fran

    2010-01-01

    Differing accounts are conventionally given of the origins of medical sociology and its parent discipline sociology. These distinct "histories" are justified on the basis that the sociological founders were uninterested in medicine, mortality and disease. This article challenges these "constructions" of the past, proposing the theorization of health not as a "late development of sociology" but an integral part of its formation. Drawing on a selection of key sociological texts, it is argued that evidence of the founders' sustained interest in the infirmities of the individual, of mortality, and in medicine, have been expunged from the historical record through processes of "canonization" and "medicalization."

  19. Genetic analysis of captive proboscis monkeys.

    PubMed

    Ogata, Mitsuaki; Seino, Satoru

    2015-01-01

    Information on the genetic relationships of captive founders is important for captive population management. In this study, we investigated DNA polymorphisms of four microsatellite loci and the mitochondrial control region sequence of five proboscis monkeys residing in a Japanese zoo as captive founders, to clarify their genetic relationship. We found that two of the five monkeys appeared to be genetically related. Furthermore, the haplotypes of the mitochondrial control region of the five monkeys were well differentiated from the haplotypes previously reported from wild populations from the northern area of Borneo, indicating a greater amount of genetic diversity in proboscis monkeys than previously reported.

  20. Efforts to establish a biological control agent against incipient infestations of Old World climbing fern in southwest Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    When available, field-adapted insects should be selected for colonization and redistribution, because they appear to offer better prospects for establishment than lab-reared insects. Small founder populations of monophagous biocontrol agents that depend on a patchy, rare host plant are susceptible t...

  1. John Tracy Clinic/University of San Diego Graduate Program: A Distance Learning Model

    ERIC Educational Resources Information Center

    McGinnis, Mary

    2010-01-01

    The John Tracy Clinic (JTC) has a long history in the development and implementation of distance education courses for parents. It began with the founder of JTC, Louise Tracy, who personally corresponded with parents of young children with hearing loss around the globe to provide them hope, guidance, and encouragement. Mrs. Tracy's correspondence…

  2. Wound care into the new millennium.

    PubMed

    Zarbock, S F

    1998-08-01

    "There has never been a time in the history of management of wounds when so many have been so well prepared to effect improvement in the quality of care being delivered at reduced costs and with improved outcomes," says Dick Meer, founder and executive director of the Center for Tissue Trauma Research and Education (CTTRE) in Jensen Beach, Fla.

  3. Benjamin Moore, Science, and Medical Planning in Early Twentieth-Century Britain

    ERIC Educational Resources Information Center

    Lawson, Gordon S.

    2008-01-01

    Benjamin Moore (1867-1922), physiologist and biochemist, was an eminent member of the British scientific and medical community in the early twentieth century. As a founder and president of the State Medical Services Association (SMSA) from its establishment in 1912 until his untimely death in 1922, Moore was a prominent medical services activist…

  4. Fast Track: A Language Arts Program for Middle School Gifted

    ERIC Educational Resources Information Center

    Schneider, Jean

    2008-01-01

    "Fast Track" is a pseudonym for an accelerated, advanced language arts program for verbally gifted and high potential students in grades 6-8. The critical thinking model used for "Fast Track" was gleaned from Coalition of Essential Schools founder Ted Sizer's Habits of Mind: significance, evidence, connections, perspective, and supposition, as…

  5. Moving beyond a Google Search: Google Earth, SketchUp, Spreadsheet, and More

    ERIC Educational Resources Information Center

    Siegle, Del

    2007-01-01

    Google has been the search engine of choice for most Web surfers for the past half decade. More recently, the creative founders of the popular search engine have been busily creating and testing a variety of useful products that will appeal to gifted learners of varying ages. The purpose of this paper is to share information about three of these…

  6. Sport-Based Youth and Community Development: Beyond the Ball in Chicago

    ERIC Educational Resources Information Center

    Jacobs, Jennifer M.; Castañeda, Amy; Castañeda, Rob

    2016-01-01

    Rob and Amy Castañeda, the co-founders of a sports/play-based youth and community development organization called Beyond the Ball (www.beyondtheball.org), cite the collaborative and dynamic nature of the TPSR Alliance as an important influence for their work. Beyond the Ball serves individuals between kindergarten and post-college, in the North…

  7. The Joy of No Sex

    ERIC Educational Resources Information Center

    Wasley, Paula

    2007-01-01

    This article reports on Justin F. Murray and Sarah M. Kinsella, the founders of a Harvard University student group called True Love Revolution that promotes the practical benefits of sexual abstinence until marriage and how Murray and Kinsella look forward to living the message after graduation. These "true love" revolutionaries cast chastity as a…

  8. RNA-guided genome editing in Drosophila with the purified Cas9 protein.

    PubMed

    Lee, Jeong-Soo; Kwak, Su-Jin; Kim, Jungeun; Kim, Ae-Kyeong; Noh, Hae Min; Kim, Jin-Soo; Yu, Kweon

    2014-07-01

    We report a method for generating Drosophila germline mutants effectively via injection of the complex of the purified Cas9 protein, tracrRNA, and gene-specific crRNAs, which may reduce delayed mutations because of the transient activity of the Cas9 protein, combined with the simple mutation detection in GO founders by the T7E1 assay. PMID:24875628

  9. New Languages of Possibility: Early Experiments in Education as Dissent

    ERIC Educational Resources Information Center

    Walsh, Brendan; Lalor, John

    2015-01-01

    This paper reviews the work of four early radical educators: the cultural nationalist Rabindranath Tagore (1861-1941), Asia's first Nobel Laureate; Bertrand Russell (1872-1970), Cambridge mathematician and philosopher; the Irish educationalist and insurgent Patrick Pearse (1879-1916) and Leonard Elmhirst (1893-1975), co-founder of Dartington Hall…

  10. Refashioning the Practicum by Emphasizing Attending and Reflective Skills

    ERIC Educational Resources Information Center

    Oprandy, Robert

    2015-01-01

    In their 1970 guidelines for teacher-preparation programs (TPPs), TESOL's founders promoted practicum experiences that include "systematic directed observation, supervised teaching practice and progressive teaching responsibilities." TPPs with field experiences as centerpieces of their programs have been more effective in meeting the…

  11. Our Little Houses: From Folly Cove to Lake Elsinore

    ERIC Educational Resources Information Center

    Poldberg, Monique

    2011-01-01

    Virginia Lee Burton was one of the first author-artists to fully integrate text with images on the printed page, captivating generations of children. She was the founder of the Folly Cove Designers, which is an artist collective known for block printed textiles and design, an artist and a writer, entwining the visual image and written word into a…

  12. Brno Studies in English. Volume Eight. Charisteria Iosepho Vachek Sexagenario Oblata (Festschrift in Honor of Josef Vachek's Sixtieth Birthday).

    ERIC Educational Resources Information Center

    Firbas, Jan, Ed.; Hladky, Josef, Ed.

    This festscrift is presented in honor of Josef Vachek, founder of the linguistic section of the Department of English and American studies of the Purkyne University. Papers in the collection represent a wide spectrum of research and thought in linguistics and the English language and are authored by the following: (1) J. Firbas, Brno; (2) M.…

  13. The Development Turn in Comparative Education

    ERIC Educational Resources Information Center

    Steiner-Khamsi, Gita

    2006-01-01

    The 1950s and 1960s were formative years for comparative education societies in different parts of the world, including the United States and Soviet Union. In need of finding a noncapitalist source of inspiration, socialist authors resorted to N. K. Krupskaia (Lenin's wife) as a discursive founder of Marxist-Leninist comparative education. Until…

  14. The Story of Women

    ERIC Educational Resources Information Center

    Grady, Marilyn L.

    2008-01-01

    In this article, the author shares Elizabeth Ann Seton's story as a woman's story. Seton was born in 1774 to a New York family. Through her work in Maryland, Seton was credited with being the founder of the parochial Catholic school system in the U.S. Seton formed a group of sisters known as the Sisters of Charity of St. Joseph. The sisters…

  15. A Cloistered Ethos? Landscapes of Learning and English Secondary Schools for Girls: An Historical Perspective

    ERIC Educational Resources Information Center

    Goodman, Joyce

    2005-01-01

    The nineteenth-century founders of academic girls' secondary schools in England often used an existing building, frequently a former dwelling-house, adding to it as resources increased and curricula developed, before moving to a purpose-built school as the venture prospered. As municipal secondary schools for girls developed in England in the wake…

  16. A History of the Children's Theatre Association of Baltimore, Maryland from 1943-1966.

    ERIC Educational Resources Information Center

    Kraus, Joanna Halpert

    A descriptive history is presented of the Children's Theatre Association of Baltimore, an independent community children's theater, focusing on the years 1943-1966, the period in which founder Isabel Burger was in office. The Association's educational goals, influence, and contribution to the community are stressed. A major portion of the research…

  17. A Portrait of Poisson: A Fish out of Water Who Found His Calling.

    ERIC Educational Resources Information Center

    Geller, B.; Bruk, Y.

    1991-01-01

    Presents a brief historical sketch of the life and work of one of the founders of modern mathematical physics. Discusses three problem-solving applications of the Poisson distribution with examples from elementary probability theory. Provides background on two of his noteworthy results from the physics of oscillations and the deformation of rigid…

  18. 25th anniversary of the Gagarin Cosmonaut Training Center

    NASA Technical Reports Server (NTRS)

    Goreglyad, I.; Shonin, G.

    1985-01-01

    Interviews with retired Major General of Aviation L. Goreglyad and pilot-cosmonaut with the 25th anniversary of the establishment of the Gagarin Cosmonaut Training Center. Major-General Goreglyad, one of the Center's founders, tells of its development. Major General Shonin, one of the first cosmonauts to train there, tells of the tests and procedures leading to his acceptance as a trainee.

  19. Native American Children's Books. Book Reviews.

    ERIC Educational Resources Information Center

    Moulton, Kathryn Elizabeth; Cornelius, Carol

    1993-01-01

    Reviews 11 children's books, published 1990-93, suitable for elementary and middle school students, covering Native riddles; Hiawatha as founder of the Iroquois confederacy; Chief Seattle's famous speech; stories about Inuit life and Mexican village life during the 1500s; Sequoyah and the Cherokee alphabet; the Iroquois creation myth; Wampanoag…

  20. Peace Amid Violence

    ERIC Educational Resources Information Center

    Overland, Martha Ann

    2007-01-01

    When the doors of the International Buddhist College opened in the southern rural province of Songkhla in Thailand after nearly a decade of hard work and planning, the founders praised the achievement as the culmination of devotion, faith, and, of course, good karma. With its rare combination of secular academics and monastic life, the college is…

  1. The Pleasures and Lessons of Academic Mythbusting: An Interview with Scott Lilienfeld

    ERIC Educational Resources Information Center

    Zinn, Tracy E.

    2010-01-01

    Scott O. Lilienfeld is a professor of psychology at Emory University, in Atlanta, Georgia. Dr. Lilienfeld is founder and editor of the journal, "Scientific Review of Mental Health Practice," and is past president of the Society for a Science of Clinical Psychology. He has been a member of 11 journal editorial boards, including the "Journal of…

  2. [History and activities of the Rescue Coordination Center].

    PubMed

    Hausman, A

    1983-01-01

    The founder and first director of the C.C.R. enumerates the principles that led to the conception and the achievement of the C.C.R. He reviews the principal rescue activities during these 25 years and mentions the development of supplementary activities on safety, ergonomics and respiratory protection during the last few years.

  3. Sites of ozone sensitivity in diverse maize inbred lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tropospheric ozone (O3) is an air pollutant that costs ~$14-26 billion in global crop losses and is projected to worsen in the future. Potential sites of O3 sensitivity in maize were tested by growing 200 inbred lines, including the nested association mapping population founder lines, under ambient...

  4. eHPE: A History of the Future

    ERIC Educational Resources Information Center

    Gard, Michael

    2014-01-01

    A grand convergence looms. It seems at least plausible that health and physical education may soon be lived by students in ways that are radically different from the past and sharply at odds with the imaginings of its founders and generations of academic aficionados. Perhaps in some respects, the differences will be superficial and less important…

  5. In Search of a "Benevolent Despot": John T. Emlen and the Establishment of the First Colored Boys' Club, 1903-1913

    ERIC Educational Resources Information Center

    Savage, Carter Julian

    2013-01-01

    This article examines the establishment and early history of the first Boys' Club for African American boys--the Wissahickon Boys' Club--through the thoughts and actions of its Quaker founder, John Thompson Emlen. The purpose of this article is not only to document the founding of this historic organization but also to describe…

  6. William Lester Bodine: The Honorary Life Presidential Years, 1917-1946

    ERIC Educational Resources Information Center

    McCullagh, James G.; Niehaus, Rebecca L.

    2007-01-01

    The primary purpose of this article is to share with the reader the beliefs, on a variety of topics, of William Lester Bodine, co-founder, first president, and first Honorary Life President of the National League of Compulsory Education Officials. The convention's annual proceedings are the source for his reflections, ideas, aspirations, and…

  7. Bribery and extortion: can restaurants help?

    PubMed

    Zucker, A

    2000-04-01

    Examples of tipping suggest that the distinction between tipping, bribery and extortion can be questioned. Some well known ideas about bribery will not work if extended to tipping and, indeed, these analyses may founder whether or not tipping, bribery and extortion merge. I suggest that more case study analysis as well as a discussion of the relationship between character and actions are needed.

  8. Credential of National Board for Professional Teaching Standards Has Impact

    ERIC Educational Resources Information Center

    Viadero, Debra; Honawar, Vaishali

    2008-01-01

    Teachers who earn advanced certification from the National Board for Professional Teaching Standards are more effective than teachers without that credential, but there is little evidence to show the program has transformed the field in the broader ways its founders envisioned, a long-awaited report released last week by a national scientific…

  9. "And This Is How You Shall Ask": Linguistics, Anthropology, and Education in the Work of David Smith

    ERIC Educational Resources Information Center

    Gilmore, Perry; McDermott, Ray

    2006-01-01

    This article celebrates the life and work of David M. Smith, former Council on Anthropology and Education president and founder of the University of Pennsylvania Ethnography in Education Research Forum, tracing his contributions to the fields of linguistics, anthropology, and education through the dual lens of his ten research principles and Walt…

  10. Charter School Autonomy: A Half-Broken Promise

    ERIC Educational Resources Information Center

    Brinson, Dana; Rosch, Jacob

    2010-01-01

    For nearly two decades, charter founders have opened schools across the land on the basis of a distinctive education bargain: operational autonomy--freedom from restrictions typically placed on public schools--in exchange for strong results-based accountability. During that time, many have studied the "results" and "accountability" side of this…

  11. A Laboratory for Public Scholarship and Democracy

    ERIC Educational Resources Information Center

    Cohen, Jeremy

    2006-01-01

    The founder of Penn State's Laboratory for Public Scholarship and Democracy and chair of Penn State's Public Scholarship Associates establishes public scholarship's connections with democracy by distinguishing public scholarship from service, outlining a curriculum of consequence, and suggesting the constitutional roots of public scholarship.

  12. Classical Influence on the Founding of the American Republic.

    ERIC Educational Resources Information Center

    Molanphy, Helen M.

    The founding fathers of the United States were products of a classical education, and they used the Greek and Roman classics as republican models and classical virtues. In their writings, the founders frequently associated liberty and republicanism with the ancient commonwealths. John Adams spoke on three separate occasions of the need to reflect…

  13. 4-H and Iowa.

    ERIC Educational Resources Information Center

    Gore, Deborah, Ed.

    1988-01-01

    This issue focuses on Iowa's role in the historical development of the 4-H youth program. "Roots in Iowa" and "Jessie Field Shambaugh: The Mother of 4-H" (J. Friedel) describes the rural Iowan roots of the 4-H program, which today is located in 80 different countries, and give the story of its founder. Jessie Shambaugh, a rural Iowa teacher and…

  14. Making room for alternatives.

    PubMed

    Edelberg, D

    1994-07-01

    Alternative healing is an idea whose time has come, and 1993 was the critical year for that recognition. So believes internist David Edelberg, founder of the Chicago Holistic Center. There patients can see one of four allopathic physicians as well as practitioners in 37 additional therapies, including acupuncture, infant massage, homeopathy, nutrition counseling, and Ayurvedic medicine. PMID:10136509

  15. Education for Everyone: Agenda for Education in a Democracy

    ERIC Educational Resources Information Center

    Goodlad, John I.; Mantle-Bromley, Corinne; Goodlad, Stephen John

    2004-01-01

    The founders of the United States envisioned education as providing for all citizens the necessary apprenticeship in the understanding and practice of democracy. To make democracy safe there must be universal schooling; to make schooling safe for education there must be democracy. But since the founding of the country, the study and practice of…

  16. Ave Maria: A 'Seriously Catholic' Law School.

    ERIC Educational Resources Information Center

    Mangan, Katherine S.

    2000-01-01

    Reports on the founding of Ave Maria School of Law (Michigan), opening in 2000, which plans to integrate Catholic teachings into every course. Focus is on the school's founder, Thomas S. Monaghan, and the school's first dean, Bernard Dobranski, who suggest that the new school can avoid difficulties with tenured liberal professors and attract top…

  17. The Middlebury College Foreign Language Schools. The Story of a Unique Idea.

    ERIC Educational Resources Information Center

    Freeman, Stephen A.

    This in-depth history of the Middlebury language schools was written as part of the celebration of the 175th anniversary of Middlebury College. Chapter one gives the general background of the schools. Chapter two discusses the founders of the German, French and Spanish schools and chapter three, the builders of the French, Spanish, German, Italian…

  18. Eta Sigma Gamma: Preparing Leaders Today for Tomorrow's Challenges

    ERIC Educational Resources Information Center

    Brown, Kelli McCormack

    2007-01-01

    There is no one definition for a leader or for leadership, but most people can identify a leader and can provide qualities of a good leader or good leadership. The founders of Eta Gamma Gamma--William Bock, Warren Schaller, and Robert Synovitz--all displayed a critical characteristic of leadership by having and acting on a vision. Leadership has…

  19. Philosophy of Hutterite Education.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    The approximately 15,000 Hutterites living in the United States and Canada have a long history of development. Their founder, Jacob Hutter, became a martyr in 1536 in what is now Czechoslovakia. From Czechoslovakia, the Hutterites moved to the Ukraine in 1770 and to the United States in 1874. Hutterite philosophy emphasizes both modern and…

  20. Becoming a "History Person" or, If Sally Says It's Possible, It Must Be

    ERIC Educational Resources Information Center

    Rowland, Nancy

    2010-01-01

    In this article, the author shares how Sally Smith, founder of The Lab School of Washington, was right about her being a "history person" when she was assigned to teach Democracy at the Lab School. The author was hired to teach Democracy in 1996, after working in the Junior High for a year as an assistant teacher. Smith explained to the author…