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Sample records for chagosensis leucettidae founder

  1. Phylogeography of western Pacific Leucetta 'chagosensis' (Porifera: Calcarea) from ribosomal DNA sequences: implications for population history and conservation of the Great Barrier Reef World Heritage Area (Australia).

    PubMed

    Wörheide, Gert; Hooper, John N A; Degnan, Bernard M

    2002-09-01

    Leucetta 'chagosensis' is a widespread calcareous sponge, occurring in shaded habitats of Indo-Pacific coral reefs. In this study we explore relationships among 19 ribosomal DNA sequence types (the ITS1-5.8S-ITS2 region plus flanking gene sequences) found among 54 individuals from 28 locations throughout the western Pacific, with focus on the Great Barrier Reef (GBR). Maximum parsimony analysis revealed phylogeographical structuring into four major clades (although not highly supported by bootstrap analysis) corresponding to the northern/central GBR with Guam and Taiwan, the southern GBR and subtropical regions south to Brisbane, Vanuatu and Indonesia. Subsequent nested clade analysis (NCA) confirmed this structure with a probability of > 95%. After NCA of geographical distances, a pattern of range expansion from the internal Indonesian clade was inferred at the total cladogram level, as the Indonesian clade was found to be the internal and therefore oldest clade. Two distinct clades were found on the GBR, which narrowly overlap geographically in a line approximately from the Whitsunday Islands to the northern Swain Reefs. At various clade levels, NCA inferred that the northern GBR clade was influenced by past fragmentation and contiguous range expansion events, presumably during/after sea level low stands in the Pleistocene, after which the northern GBR might have been recolonized from the Queensland Plateau in the Coral Sea. The southern GBR clade is most closely related to subtropical L. 'chagosensis', and we infer that the southern GBR probably was recolonized from there after sea level low stands, based on our NCA results and supported by oceanographic data. Our results have important implications for conservation and management of the GBR, as they highlight the importance of marginal transition zones in the generation and maintenance of species rich zones, such as the Great Barrier Reef World Heritage Area.

  2. 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.

  3. Founder of cosmonautics

    NASA Astrophysics Data System (ADS)

    Maksimov, A. I.

    2007-09-01

    The paper described the creative path of K.E. Tsiolkovsky, the founder of theoretical cosmonautics, who devoted his life to solving various problems in the field of aerodynamics and rocket engineering, creating dirigibles with a metallic shell, jet planes, and air-cushioned trains, and studying the origin of planets, the Sun, and the Universe. The main engineering proposals of a scientist of great originality, which found applications in modern rocket and space engineering, are briefly analysed. The versatility of his interests is demonstrated; his research is shown to deal with many fields of science and technology, including the kinetic theory of gases, geology, cosmology, biology, philosophy, sociology, theology, and language science.

  4. Founders of the Social Studies.

    ERIC Educational Resources Information Center

    Weakland, John E., Ed.

    1986-01-01

    Presents educational biographies of Henry Johnson, I. James Quillen, Lawrence E. Metcalf, and Shirley Engle; all considered founders of the social studies. Additional articles on defining the social studies, problem solving, and mentoring are included in this issue. (JDH)

  5. Trichohepatoenteric syndrome: founder mutation in asian indians.

    PubMed

    Kotecha, U H; Movva, S; Puri, R D; Verma, I C

    2012-08-01

    Trichohepatoenteric syndrome (THES) is characterized by chronic diarrhea, dysmorphic facies and hair abnormalities. Hepatic involvement varies from no abnormality to cirrhosis and hemochromatosis. Recently, mutations in the tetratricopeptide repeat domain 37 (TTC37) gene were identified to cause THES. The c.2808G>A variation was suggested as a possible founder mutation among the South Asians. We further report 2 unrelated cases of Asian-Indian ethnicity (Gujrati) with THES, wherein targeted mutation analysis revealed the same mutation in homozygous form in both cases. These findings, as well as haplotype analysis, corroborate the founder mutation hypothesis amongst Asian Indo-Pakistani ethnic groups. A restriction enzyme-based method is also described to identify this founder mutation. One of our probands had multiple hepatic hemangiomas, a feature not previously observed in this syndrome.

  6. 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 the…

  7. Differentiating founder and chronic HIV envelope sequences.

    PubMed

    Murray, John M; Maher, Stephen; Mota, Talia; Suzuki, Kazuo; Kelleher, Anthony D; Center, Rob J; Purcell, Damian

    2017-01-01

    Significant progress has been made in characterizing broadly neutralizing antibodies against the HIV envelope glycoprotein Env, but an effective vaccine has proven elusive. Vaccine development would be facilitated if common features of early founder virus required for transmission could be identified. Here we employ a combination of bioinformatic and operations research methods to determine the most prevalent features that distinguish 78 subtype B and 55 subtype C founder Env sequences from an equal number of chronic sequences. There were a number of equivalent optimal networks (based on the fewest covarying amino acid (AA) pairs or a measure of maximal covariance) that separated founders from chronics: 13 pairs for subtype B and 75 for subtype C. Every subtype B optimal solution contained the founder pairs 178-346 Asn-Val, 232-236 Thr-Ser, 240-340 Lys-Lys, 279-315 Asp-Lys, 291-792 Ala-Ile, 322-347 Asp-Thr, 535-620 Leu-Asp, 742-837 Arg-Phe, and 750-836 Asp-Ile; the most common optimal pairs for subtype C were 644-781 Lys-Ala (74 of 75 networks), 133-287 Ala-Gln (73/75) and 307-337 Ile-Gln (73/75). No pair was present in all optimal subtype C solutions highlighting the difficulty in targeting transmission with a single vaccine strain. Relative to the size of its domain (0.35% of Env), the α4β7 binding site occurred most frequently among optimal pairs, especially for subtype C: 4.2% of optimal pairs (1.2% for subtype B). Early sequences from 5 subtype B pre-seroconverters each exhibited at least one clone containing an optimal feature 553-624 (Ser-Asn), 724-747 (Arg-Arg), or 46-293 (Arg-Glu).

  8. Differentiating founder and chronic HIV envelope sequences

    PubMed Central

    Maher, Stephen; Mota, Talia; Suzuki, Kazuo; Kelleher, Anthony D.

    2017-01-01

    Significant progress has been made in characterizing broadly neutralizing antibodies against the HIV envelope glycoprotein Env, but an effective vaccine has proven elusive. Vaccine development would be facilitated if common features of early founder virus required for transmission could be identified. Here we employ a combination of bioinformatic and operations research methods to determine the most prevalent features that distinguish 78 subtype B and 55 subtype C founder Env sequences from an equal number of chronic sequences. There were a number of equivalent optimal networks (based on the fewest covarying amino acid (AA) pairs or a measure of maximal covariance) that separated founders from chronics: 13 pairs for subtype B and 75 for subtype C. Every subtype B optimal solution contained the founder pairs 178–346 Asn-Val, 232–236 Thr-Ser, 240–340 Lys-Lys, 279–315 Asp-Lys, 291–792 Ala-Ile, 322–347 Asp-Thr, 535–620 Leu-Asp, 742–837 Arg-Phe, and 750–836 Asp-Ile; the most common optimal pairs for subtype C were 644–781 Lys-Ala (74 of 75 networks), 133–287 Ala-Gln (73/75) and 307–337 Ile-Gln (73/75). No pair was present in all optimal subtype C solutions highlighting the difficulty in targeting transmission with a single vaccine strain. Relative to the size of its domain (0.35% of Env), the α4β7 binding site occurred most frequently among optimal pairs, especially for subtype C: 4.2% of optimal pairs (1.2% for subtype B). Early sequences from 5 subtype B pre-seroconverters each exhibited at least one clone containing an optimal feature 553–624 (Ser-Asn), 724–747 (Arg-Arg), or 46–293 (Arg-Glu). PMID:28187204

  9. 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

  10. Founder mitochondrial haplotypes in Amerindian populations.

    PubMed

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

    1994-07-01

    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.

  11. 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.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22456885

  13. 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…

  14. 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...

  15. GNE Myopathy: Two Clusters with History and Several Founder Mutations

    PubMed Central

    Argov, Zohar; Mitrani Rosenbaum, Stella

    2015-01-01

    Abstract GNE myopathy (previous names: HIBM, DMRV, IBM2) is a unique distal myopathy with quadriceps sparing. This recessively inherited myopathy has been diagnosed in various regions of the world with more than 150 disease-causing mutations already identified. Several of those are proven or suspected to be founder mutations in certain regional clusters and are described in this review. The review also discusses some historical aspects that might be relevant to the mutational distribution. PMID:27858758

  16. Founder mutations in BRCA1 and BRCA2 genes.

    PubMed

    Ferla, R; Calò, V; Cascio, S; Rinaldi, G; Badalamenti, G; Carreca, I; Surmacz, E; Colucci, G; Bazan, V; Russo, A

    2007-06-01

    BRCA1 and BRCA2 germline mutations contribute to a significant number of familial and hereditary breast and/or ovarian cancers. The proportion of high-risk families with breast and/or ovarian cancer cases due to mutations in these tumor suppressor genes varies widely among populations. In some population, a wide spectrum of different mutations in both genes are present, whereas in other groups specific mutations in BRCA1 and BRCA2 have been reported with high frequency. Most of these mutations are prevalent in restricted populations as consequence of a founder effect. The comparison of haplotypes between families with the same mutation can distinguish whether high-frequency alleles derive from an older or more recent single mutational event or whether they have arisen independently more than once. Here, we review some of the most well-known and significant examples of founder mutations in BRCA genes found in European and non-European populations. In conclusion, the identification of the ethnic group of families undergoing genetic counseling enables the geneticist and oncologist to make more specific choices, leading to simplify the clinical approach to genetic testing carried out on members of high-risk families. Futhermore, the high frequency of founder mutations, allowing to analyze a large number of cases, might provide accurate information regarding their penetrance.

  17. 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.

  18. Bounds of foundering in the southern Sierra Nevada

    NASA Astrophysics Data System (ADS)

    Gilbert, H.; Yang, Y.; Forsyth, D. W.; Jones, C. H.; Owens, T. J.; Zandt, G.

    2008-12-01

    Previous petrologic and tomographic observations have found that while a thick residual root formed under the southern Sierra Nevada batholith, it has since foundered and descends into the mantle. The recent Sierra Nevada EarthScope Project (SNEP) FlexArray in eastern California sought to improve our understanding of the mechanism, extent, and tectonic consequences of this process. Over fifty broadband seismic stations deployed between 2005 and 2007 comprised the SNEP array. Many of these stations were redeployed once to occupy ~100 sites spanning much of the mountain range. Surrounding stations from the TransportableArray provide a common reference for analyzing SNEP stations that moved. Using fundamental mode Rayleigh waves, generated by teleseismic earthquakes at periods between 20 and 100 s, we examine lithospheric structures beyond the crust into the mantle. By employing an array processing approach, and treating the incoming surface wave field as two interfering plane waves (Forsyth and Li, 2005), we account for multipathing and scattering of the wave field, which is common along continental margins and within mountain ranges. The 25 km station spacing of the SNEP deployment allows for features to be resolved that could not be found using only the TransportableArray. For periods between 20 and 50 s that are sensitive structures in the crust and uppermost mantle, the pattern of phase velocities along the southern Sierra Nevada exhibits a similar asymmetry to that found for crustal structures. Within this period range, low phase velocities characterize regions of thin crust of the southeastern Sierra and extend out to Walker Lane and the western Basin and Range. Conversely, the western foothills possess thicker crust and higher phase velocities. In the central Sierra, at latitudes near Lake Tahoe, the distribution of anomalies changes and the low and the high phase velocities that mark the eastern and western sides of the southern Sierra terminate. These

  19. Fragile X founder effects and new mutations in Finland

    SciTech Connect

    Zhong, N.; Smits, B.; Curley, D.

    1996-07-12

    The apparent associations between fragile X mutations and nearby microsatellites may reflect both founder effects and microsatellite instability. To gain further insight into their relative contributions, we typed a sample of 56 unrelated control and 37 fragile X chromosomes from an eastern Finnish population for FMR1 CGG repeat lengths, AGG interspersion patterns, DXS548, FRAXAC1, FRAXE and a new polymorphic locus, Alu-L. In the controls, the most common FMR1 allele was 30 repeats with a range of 20 to 47 and a calculated heterozygosity of 88%. A strong founder effect was observed for locus DXS548 with 95% of fragile X chromosomes having the 21 CA repeat (196 bp) allele compared to 17% of controls, while none of the fragile X but 69% of controls had the 20 repeat allele. Analysis of the combined loci DXS548-FRAXAC1-FRAXE showed three founder haplotypes. Haplotype 21-19-16 was found on 27 (75%) of fragile X chromosomes but on none of controls. Three (8.4%) fragile X chromosomes had haplotypes 21-19-15, 21-19-20, and 21-19-25 differing from the common fragile X haplotype only in FRAXE. These could have arisen by recombination or from mutations of FRAXE. A second haplotype 21-18-17 was found in four (11.1%) fragile X chromosomes but only one (1.9%) control. This may represent a more recent founder mutation. A third haplotype 25-21-15, seen in two fragile X chromosomes (5.6%) and one (1.9%) control, was even less common and thus may represent an even more recent mutation or admixture of immigrant types. Analysis of the AGG interspersions within the FMR1 CGG repeat showed that 7/8 premutation chromosomes lacked an AGG whereas all controls had at least one AGG. This supports the hypothesis that the mutation of AGG to CGG leads to repeat instability and mutational expansion. 43 refs., 3 figs., 7 tabs.

  20. Identification of a founder BRCA2 mutation in Sardinia

    PubMed Central

    Pisano, M; Cossu, A; Persico, I; Palmieri, G; Angius, A; Casu, G; Palomba, G; Sarobba, M G; Rocca, P C Ossu; Dedola, M F; Olmeo, N; Pasca, A; Budroni, M; Marras, V; Pisano, A; Farris, A; Massarelli, G; Pirastu, M; Tanda, Francesco

    2000-01-01

    Sardinian population can be instrumental in defining the molecular basis of cancer, using the identity-by-descent method. We selected seven Sardinian breast cancer families originating from the northern-central part of the island with multiple affected members in different generations. We genotyped 106 members of the seven families and 20 control nuclear families with markers flanking BRCA2 locus at 13q12–q13. The detection of a common haplotype shared by four out of seven families (60%) suggests the presence of a founder BRCA2 mutation. Direct sequencing of BRCA2 coding exons of patients carrying the shared haplotype, allowed the identification of a ‘frame-shift’ mutation at codon 2867 (8765delAG), causing a premature termination-codon. This mutation was found in breast cancer patients as well as one prostate and one bladder cancer patient with shared haplotype. We then investigated the frequency of 8765delAG in the Sardinian breast cancer population by analysing 270 paraffin-embedded normal tissue samples from breast cancer patients. Five patients (1.7%) were found to be positive for the 8765delAG mutation. Discovery of a founder mutation in Sardinia through the identity-by-descent method demonstrates that this approach can be applied successfully to find mutations either for breast cancer or for other types of tumours. © 2000 Cancer Research Campaign PMID:10682665

  1. 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.

  2. Founder mutation for Huntington disease in Caucasus Jews.

    PubMed

    Melamed, O; Behar, D M; Bram, C; Magal, N; Pras, E; Reznik-Wolf, H; Borochowitz, Z U; Davidov, B; Mor-Cohen, R; Baris, H N

    2015-02-01

    Huntington disease (HD), an autosomal dominant disorder involving HTT, is characterized by chorea, psychiatric illness and cognitive decline. Diagnosis and age of onset depend on the degree of expansion of the trinucleotide CAG repeat within the gene. The prevalence of HD is known for Europeans but has not been studied in the Israeli population. Between 2006 and 2011 we diagnosed in our adult genetics clinic ten HD probands, nine of whom were Caucasus Jews (CJ) (Azerbaijani), and one Ashkenazi Jewish. We performed haplotype analysis to look for evidence of a founder mutation, and found that of the nine CJ, eight shared the same haplotype that was compatible with the A1 haplogroup. We calculated the coalescence age of the mutation to be between 80 and 150 years. Ninety percent of our HD patients are CJ, as are 27% of the HD patients in Israel, although the CJ comprise only 1.4% of the Israeli population. Our findings suggest a higher prevalence of HD among CJ compared to the general Israeli population and are consistent with a recent founder mutation. We recommend a higher degree of suspicion for HD in CJ with subtle clinical findings.

  3. 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

    2013-06-04

    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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23696661

  5. [Identification and characterization of HIV-1 transmitted /founder viruses].

    PubMed

    Jianyuan, Zhao; Jiwei, Ding; Zeyun, Mi; Tao, Wei; Shan, Cen

    2015-05-01

    During the spread of human immunodeficiency virus type 1 (HIV-1) in the mucosa, the entire genetic diversity of the viruses is significantly reduced. The vast majority of HIV-1 mucosal infections are established by one or a few viruses and ultimately develop into systemic infections, thus the initial virus is called transmitted/founder virus (T/F virus). The study of T/F virus will benefit understanding its key characteristics resulting in successful viral replication in the new host body, which may provide novel strategies for the development of AIDS vaccines, pre-exposure prophylaxis and other therapeutic interventions. In this review, we summarize the discovery and evolutionary characteristics of T/F virus as well as early immune response after HIV-1 infection, which will establish the basis to explore the features of T/F viruses.

  6. 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.

  7. 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

  8. 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.

  9. Multipoint likelihoods for genetic linkage: The untyped founder problem

    SciTech Connect

    O`Connell, J.R.; Chiarulli, D.M.; Weeks, D.E.

    1994-09-01

    Too many untyped founders in a pedigree cause the Elston-Stewart algorithm to grind to a halt. Our solution to this problem involves recoding alleles based on symmetry and identity-by-descent to greatly reduce the number of multi-locus genotypes. We also use modified genotype elimination to better organize the calculation, substantially reducing the amount of memory needed. We never have to consider multi-locus genotypes that are not valid. Thus for typed pedigrees, the calculation is independent of the number of alleles at a locus. In addition, our locus-by-locus method allows us to group similar calculations to avoid recomputation, costly bookkeeping for valid genotypes, and large memory allocation. We were able to do a 4-locus likelihood for a 41-member simple pedigree with the first two generations untyped and an allele product of over 1500 in under an hour. This likelihood cannot be computed at all with LINKAGE, since some of its arrays would require over a gigabyte of memory. Our locus-by-locus method is also well-suited for parallelization since we can factor the computation into smaller independent pieces. This will enable us to tackle problems of even greater complexity.

  10. 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.

  11. Founder effect in spinal and bulbar muscular atrophy (SBMA).

    PubMed

    Tanaka, F; Doyu, M; Ito, Y; Matsumoto, M; Mitsuma, T; Abe, K; Aoki, M; Itoyama, Y; Fischbeck, K H; Sobue, G

    1996-09-01

    We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X chromosomes and 173 control X chromosomes in Japanese males. The control chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32 repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/- 3 copies. The control chromosomes had seven different alleles of the (GGC)n repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%), while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distribution was significantly different between SBMA and control chromosomes (P < 0.0001), indicating the presence of linkage disequilibrium. There was no allelic association between the (CAG)n and (GGC)n microsatellites among control subjects as well as SBMA patients, which suggests that a founder effect makes a more significant contribution to generation of Japanese SBMA chromosomes than new mutations.

  12. Drosophila Heartless Acts with Heartbroken/Dof in Muscle Founder Differentiation

    PubMed Central

    Dutta, Devkanya; Shaw, Sanjeev; Maqbool, Tariq; Pandya, Hetal

    2005-01-01

    The formation of a multi-nucleate myofibre is directed, in Drosophila, by a founder cell. In the embryo, founders are selected by Notch-mediated lateral inhibition, while during adult myogenesis this mechanism of selection does not appear to operate. We show, in the muscles of the adult abdomen, that the Fibroblast growth factor pathway mediates founder cell choice in a novel manner. We suggest that the developmental patterns of Heartbroken/Dof and Sprouty result in defining the domain and timing of activation of the Fibroblast growth factor receptor Heartless in specific myoblasts, thereby converting them into founder cells. Our results point to a way in which muscle differentiation could be initiated and define a critical developmental function for Heartbroken/Dof in myogenesis. PMID:16207075

  13. 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

  14. The Slavic NBN Founder Mutation: A Role for Reproductive Fitness?

    PubMed Central

    Seemanova, Eva; Varon, Raymonda; Vejvalka, Jan; Seeman, Pavel; Chrzanowska, Krystyna H.; Digweed, Martin; Resnick, Igor; Kremensky, Ivo; Saar, Kathrin; Hoffmann, Katrin; Dutrannoy, Véronique; Karbasiyan, Mohsen; Ghani, Mehdi; Barić, Ivo; Tekin, Mustafa; Kovacs, Peter; Krawczak, Michael; Reis, André; Sperling, Karl

    2016-01-01

    The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657del5 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c.657del5 of 0.5% to 1% as observed in different Slavic populations because deleterious mutations would be eliminated quite rapidly by purifying selection. Therefore, we propose that heterozygous c.657del5 carriers have increased reproductive success, i.e., that the mutation confers heterozygote advantage. In fact, in our cohort study of the reproductive history of 24 NBS pedigrees from the Czech Republic, we observed that female carriers gave birth to more children on average than female non-carriers, while no such reproductive differences were observed for males. We also estimate that c.657del5 likely occurred less than 300 generations ago, thus supporting the view that the original mutation predated the historic split and subsequent spread of the ‘Slavic people’. We surmise that the higher fertility of female c.657del5 carriers reflects a lower miscarriage rate in these women, thereby reflecting the role of the NBN gene product, nibrin, in the repair of DNA double strand breaks and their processing in immune gene rearrangements, telomere maintenance, and meiotic recombination, akin to the previously described role of the DNA repair genes BRCA1 and BRCA2. PMID:27936167

  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. Phonemic diversity supports a serial founder effect model of language expansion from Africa.

    PubMed

    Atkinson, Quentin D

    2011-04-15

    Human genetic and phenotypic diversity declines with distance from Africa, as predicted by a serial founder effect in which successive population bottlenecks during range expansion progressively reduce diversity, underpinning support for an African origin of modern humans. Recent work suggests that a similar founder effect may operate on human culture and language. Here I show that the number of phonemes used in a global sample of 504 languages is also clinal and fits a serial founder-effect model of expansion from an inferred origin in Africa. This result, which is not explained by more recent demographic history, local language diversity, or statistical non-independence within language families, points to parallel mechanisms shaping genetic and linguistic diversity and supports an African origin of modern human languages.

  17. Genetics of murine craniofacial morphology: Diallel analysis of the eight founders of the Collaborative Cross

    PubMed Central

    Percival, Christopher J.; Liberton, Denise K.; de Villena, Fernando Pardo-Manuel; Spritz, Richard; Marcucio, Ralph

    2016-01-01

    Summary Using eight inbred founder strains of the mouse Collaborative Cross (CC) project and their reciprocal F1 hybrids, we quantified variation in craniofacial morphology across mouse strains, explored genetic contributions to craniofacial variation that distinguish the founder strains, and tested whether specific or summary measures of craniofacial shape display stronger additive genetic contributions. This study thus provides critical information about phenotypic diversity among CC founder strains and about the genetic contributions to this phenotypic diversity, which is relevant to understanding the basis of variation in standard laboratory strains and natural populations. Craniofacial shape was quantified as a series of size-adjusted linear dimensions (RDs) and by principal components (PC) analysis of morphological landmarks captured from computed tomography images from 62 out of the 64 reciprocal crosses of the CC founder strains. We first identified aspects of skull morphology that vary between these phenotypically ‘normal’ founder strains and that are defining characteristics of these strains. We estimated the contributions of additive and various non-additive genetic factors to phenotypic variation using diallel analyses of a subset of these strongly differing RDs and the first 8 PCs of skull shape variation. We find little difference in the genetic contributions to RD measures and PC scores, suggesting fundamental similarities in the magnitude of genetic contributions to both specific and summary measures of craniofacial phenotypes. Our results indicate that there are stronger additive genetic effects associated with defining phenotypic characteristics of specific founder strains, suggesting these distinguishing measures are good candidates for use in genotype-phenotype association studies of CC mice. Our results add significantly to understanding of genotype-phenotype associations in the skull, which serve as a foundation for modeling the origins of

  18. 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

  19. The Influence of Founder Type on Charter School Structures and Operations.

    ERIC Educational Resources Information Center

    Henig, Jeffrey R.; Holyoke, Thomas T.; Brown, Heath; Lacireno-Paquet, Natalie

    Much of the literature on charter schools treats them as an undifferentiated mass. A typology of charter schools grounded in the norms, traditions, and perspectives of the founding organization or organizers is presented and tested in this paper. It is suggested that there are two broad categories of charter founders: (1) those who are more…

  20. The Influence of Founder Type on Charter School Structures and Operations

    ERIC Educational Resources Information Center

    Henig, Jeffrey R.; Holyoke, Thomas T.; Brown, Heath; Lacireno-Paquet, Natalie

    2005-01-01

    Much of the literature on charter schools treats them as an undifferentiated mass. Here we present and test a typology of charter schools that is grounded in the norms, traditions, and perspectives of the founding organization or organizers. We suggest that there are two broad categories of charter founders--those who are more mission oriented and…

  1. Clovis Vincent (1879-1947): founder of French neurosurgery and promoter of oncologic neurosurgery.

    PubMed

    Karamanou, M; Androutsos, G; Lymperi, M; Stamboulis, E; Liappas, I; Lykouras, E

    2012-01-01

    The eminent neurologist Clovis Vincent decided to become neurosurgeon at an advanced age. His is considered the founder of French neurosurgery and the Europe's first neurosurgeon. He was mainly interested in pituitary tumors and his work on oncologic neurosurgery remains valuable.

  2. Ideas of the Founders on Constitutional Government: Resources for Teachers of History and Government.

    ERIC Educational Resources Information Center

    Patrick, John J., Ed.

    The political ideas of John Adams, Alexander Hamilton, John Jay, Thomas Jefferson, James Madison, and other Founders of the United States have been a rich civic legacy for successive generations of citizens. An important means of ensuring that these ideas on constitutional government continue to inspire and guide people in the 21st century lies in…

  3. 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…

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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)

  9. 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)

  10. Founder effects, inbreeding, and loss of genetic diversity in four avian reintroduction programs.

    PubMed

    Jamieson, Ian G

    2011-02-01

    The number of individuals translocated and released as part of a reintroduction is often small, as is the final established population, because the reintroduction site is typically small. Small founder and small resulting populations can result in population bottlenecks, which are associated with increased rates of inbreeding and loss of genetic diversity, both of which can affect the long-term viability of reintroduced populations. I used information derived from pedigrees of four monogamous bird species reintroduced onto two different islands (220 and 259 ha) in New Zealand to compare the pattern of inbreeding and loss of genetic diversity among the reintroduced populations. Although reintroduced populations founded with few individuals had higher levels of inbreeding, as predicted, other factors, including biased sex ratio and skewed breeding success, contributed to high levels of inbreeding and loss of genetic diversity. Of the 10-58 individuals released, 4-25 genetic founders contributed at least one living descendent and yielded approximately 3-11 founder-genome equivalents (number of genetic founders assuming an equal contribution of offspring and no random loss of alleles across generations) after seven breeding seasons. This range is much lower than the 20 founder-genome equivalents recommended for captive-bred populations. Although the level of inbreeding in one reintroduced population initially reached three times that of a closely related species, the long-term estimated rate of inbreeding of this one population was approximately one-third that of the other species due to differences in carrying capacities of the respective reintroduction sites. The increasing number of reintroductions to suitable areas that are smaller than those I examined here suggests that it might be useful to develop long-term strategies and guidelines for reintroduction programs, which would minimize inbreeding and maintain genetic diversity.

  11. Stereotypic founder cell patterning and embryonic muscle formation in Drosophila require nautilus (MyoD) gene function

    PubMed Central

    Wei, Qin; Rong, Yikang; Paterson, Bruce M.

    2007-01-01

    nautilus is the only MyoD-related gene in Drosophila. Nautilus expression begins around stage 9 at full germ-band extension in a subset of mesodermal cells organized in a stereotypic pattern in each hemisegment. The muscle founder cell marker Duf-LacZ, produced by the enhancer trap line rP298LacZ, is coexpressed in numerous Nautilus-positive cells when founders first appear. Founders entrain muscle identity through the restricted expression of transcription factors such as S59, eve, and Kr, all of which are observed in subsets of the nautilus expressing founders. We inactivated the nautilus gene using homology-directed gene targeting and Gal4/UAS regulated RNAi to determine whether loss of nautilus gene activity affected founder cell function. Both methods produced a range of defects that included embryonic muscle disruption, reduced viability and female sterility, which could be rescued by hsp70-nautilus cDNA transgenes. Our results demonstrate Nautilus expression marks early founders that give rise to diverse muscle groups in the embryo, and that nautilus gene activity is required to seed the correct founder myoblast pattern that prefigures the muscle fiber arrangement during embryonic development. PMID:17376873

  12. 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.

  13. G130V, a common FRDA point mutation, appears to have arisen from a common founder.

    PubMed

    Delatycki, M B; Knight, M; Koenig, M; Cossée, M; Williamson, R; Forrest, S M

    1999-10-01

    Friedreich ataxia (FRDA) is the most common inherited ataxia. About 98% of mutant alleles have an expansion of a GAA trinucleotide repeat in intron 1 of the affected gene, FRDA. The other 2% are point mutations. Of the 17 point mutations so far described, three appear to be more common. One of these is the G130V mutation in exon 4 of FRDA. G130V, when present with an expanded GAA repeat on the other allele, is associated with an atypical FRDA phenotype. Haplotype analysis was undertaken on the four families who have been described with this mutation. The results suggest a common founder for this mutation. Although marked differences in extragenic marker haplotypes were seen in one family, similar intragenic haplotyping suggests the same mutation founder for this family with the differences explicable by two recombination events.

  14. 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

  15. Chromosome 9 ALS and FTD locus is probably derived from a single founder.

    PubMed

    Mok, Kin; Traynor, Bryan J; Schymick, Jennifer; Tienari, Pentti J; Laaksovirta, Hannu; Peuralinna, Terhi; Myllykangas, Liisa; Chiò, Adriano; Shatunov, Aleksey; Boeve, Bradley F; Boxer, Adam L; DeJesus-Hernandez, Mariely; Mackenzie, Ian R; Waite, Adrian; Williams, Nigel; Morris, Huw R; Simón-Sánchez, Javier; van Swieten, John C; Heutink, Peter; Restagno, Gabriella; Mora, Gabriele; Morrison, Karen E; Shaw, Pamela J; Rollinson, Pamela Sara; Al-Chalabi, Ammar; Rademakers, Rosa; Pickering-Brown, Stuart; Orrell, Richard W; Nalls, Michael A; Hardy, John

    2012-01-01

    We and others have recently reported an association between amyotrophic lateral sclerosis (ALS) and single nucleotide polymorphisms on chromosome 9p21 in several populations. Here we show that the associated haplotype is the same in all populations and that several families previously shown to have genetic linkage to this region also share this haplotype. The most parsimonious explanation of these data are that there is a single founder for this form of disease.

  16. Twin Town in South Brazil: A Nazi's Experiment or a Genetic Founder Effect?

    PubMed Central

    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. PMID:21687665

  17. Ancient founder mutation is responsible for Imerslund-Gräsbeck Syndrome among diverse ethnicities

    PubMed Central

    2011-01-01

    Background Imerslund-Gräsbeck syndrome (IGS) was described just over 50 years ago by Olga Imerslund and Ralph Gräsbeck and colleagues. IGS is caused by specific malabsorption of cobalamin (Cbl) due to bi-allelic mutations in either the cubilin gene (CUBN) or the human amnionless homolog (AMN). Mutations in the two genes are commonly seen in founder populations or in societies with a high degree of consanguineous marriages. One particular mutation in AMN, c.208-2A>G, causing an out-of-frame loss of exon 4 in the mRNA, is responsible for some 15% of IGS cases globally. We present evidence that this founder mutation causes a substantial percentage of cases among diverse ethnicities and that the mutation is as old as human civilization. Methods Partial genotyping indicated a founder event but its presence in diverse peoples of Arabic, Turkish, Jewish, and Hispanic ancestry suggested that the mutation might be recurrent. We therefore studied the flanking sequence spanning 3.5 Mb to elucidate the origin of the haplotype and estimate the age of the mutation using a Bayesian inference method based on observed linkage disequilibrium. Results The mutation's distribution, the size of the shared haplotype, and estimates of growth rate and carrier frequency indicated that the mutation was a single prehistoric event. Dating back to the ancient Middle East around 11,600 BC, the mutation predates the advent of writing, farming, and the monotheistic religions of the region. Conclusions This mutation causes over 50% of the IGS cases among Arabic, Turkish, and Sephardic Jewish families, making it a primary target for genetic screening among diverse IGS cases originating from the Middle East. Thus, rare founder mutations may cause a substantial number of cases, even among diverse ethnicities not usually thought to be related. PMID:22078000

  18. Characterization of two Ashkenazi Jewish founder mutations in MSH6 gene causing Lynch syndrome

    PubMed Central

    Raskin, Leon; Schwenter, Frank; Freytsis, Marina; Tischkowitz, Marc; Wong, Nora; Chong, George; Narod, Steven A.; Levine, Douglas A.; Bogomolniy, Faina; Aronson, Melyssa; Thibodeau, Stephen N.; Hunt, Katherine S.; Rennert, Gad; Gallinger, Steven; Gruber, Stephen B.; Foulkes, William D.

    2015-01-01

    Founder mutations are an important cause of Lynch syndrome and facilitate genetic testing in specific ethnic populations. Two putative founder mutations in MSH6 were analyzed in 2685 colorectal cancer (CRC) cases, 337 endometrial cancer (EnCa) cases and 3310 healthy controls of Ashkenazi Jewish (AJ) descent from population-based and hospital-based case-control studies in Israel, Canada and the USA. The carriers were haplotyped and the age of the mutations was estimated. MSH6*c.3984_3987dupGTCA was found in 8/2685 CRC cases, 2/337 EnCa cases, and 1/3310 controls, consistent with a high risk of CRC (odds ratio (OR) = 9.9, 95% confidence interval (CI) = 1.2–78.9, p=0.0079) and a very high risk of EnCa (OR = 19.6, 95%CI = 1.8–217.2, p = 0.0006). MSH6*c.3959_3962delCAAG was identified in 3/2685 CRC cases, 2/337 EnCa cases and no controls. Each mutation was associated with separate conserved haplotypes. MSH6*c.3984_3987dupGTCA and MSH6*c.3959_3962delCAAG likely arose around 585 CE and 685 CE respectively. No carriers were identified in Sephardi Jews (450 cases and 490 controls). Truncating mutations MSH6*c.3984_3987dupGTCA and MSH6*c.3959_3962delCAAG cause Lynch syndrome and are founder mutations in Ashkenazi Jews. Together with other AJ founder mutations, they contribute substantially to the incidence of CRC and EnCa and are important tools for the early diagnosis and appropriate management of AJ Lynch syndrome patients. PMID:21155762

  19. The Sex Determination Gene Shows No Founder Effect in the Giant Honey Bee, Apis dorsata

    PubMed Central

    Yan, Wei Yu; Wu, Xiao Bo; Zeng, Zhi Jiang; Huang, Zachary Y.

    2012-01-01

    Background All honey bee species (Apis spp) share the same sex determination mechanism using the complementary sex determination (csd) gene. Only individuals heterogeneous at the csd allele develop into females, and the homozygous develop into diploid males, which do not survive. The honeybees are therefore under selection pressure to generate new csd alleles. Previous studies have shown that the csd gene is under balancing selection. We hypothesize that due to the long separation from the mainland of Hainan Island, China, that the giant honey bees (Apis dorsata) should show a founder effect for the csd gene, with many different alleles clustered together, and these would be absent on the mainland. Methodology/Principal Findings We sampled A. dorsata workers from both Hainan and Guangxi Provinces and then cloned and sequenced region 3 of the csd gene and constructed phylogenetic trees. We failed to find any clustering of the csd alleles according to their geographical origin, i.e. the Hainan and Guangxi samples did not form separate clades. Further analysis by including previously published csd sequences also failed to show any clade-forming in both the Philippines and Malaysia. Conclusions/Significance Results from this study and those from previous studies did not support the expectations of a founder effect. We conclude that because of the extremely high mating frequency of A. dorsata queens, a founder effect does not apply in this species. PMID:22511940

  20. Clinical applications and implications of common and founder mutations in Indian subpopulations.

    PubMed

    Ankala, Arunkanth; Tamhankar, Parag M; Valencia, C Alexander; Rayam, Krishna K; Kumar, Manisha M; Hegde, Madhuri R

    2015-01-01

    South Asian Indians represent a sixth of the world's population and are a racially, geographically, and genetically diverse people. Their unique anthropological structure, prevailing caste system, and ancient religious practices have all impacted the genetic composition of most of the current-day Indian population. With the evolving socio-religious and economic activities of the subsects and castes, endogamous and consanguineous marriages became a commonplace. Consequently, the frequency of founder mutations and the burden of heritable genetic disorders rose significantly. Specifically, the incidence of certain autosomal-recessive disorders is relatively high in select Indian subpopulations and communities that share common recent ancestry. Although today clinical genetics and molecular diagnostic services are making inroads in India, the high costs associated with the technology and the tests often keep patients from an exact molecular diagnosis, making more customized and tailored tests, such as those interrogating the most common and founder mutations or those that cater to select sects within the population, highly attractive. These tests offer a quick first-hand affordable diagnostic and carrier screening tool. Here, we provide a comprehensive catalog of known common mutations and founder mutations in the Indian population and discuss them from a molecular, clinical, and historical perspective.

  1. FKRP mutations, including a founder mutation, cause phenotype variability in Chinese patients with dystroglycanopathies.

    PubMed

    Fu, Xiaona; Yang, Haipo; Wei, Cuijie; Jiao, Hui; Wang, Shuo; Yang, Yanling; Han, Chunxi; Wu, Xiru; Xiong, Hui

    2016-12-01

    Mutations in the fukutin-related protein (FKRP) gene have been associated with dystroglycanopathies, which are common in Europe but rare in Asia. Our study aimed to retrospectively analyze and characterize the clinical, myopathological and genetic features of 12 Chinese patients with FKRP mutations. Three patients were diagnosed with congenital muscular dystrophy type 1C (MDC1C) and nine patients were diagnosed with limb girdle muscular dystrophy type 2I (LGMD2I). Three muscle biopsy specimens had dystrophic changes and reduced glycosylated α-dystroglycan staining, and two showed reduced expression of laminin α2. Two known and 13 novel mutations were identified in our single center cohort. Interestingly, the c.545A>G mutation was found in eight of the nine LGMD2I patients as a founder mutation and this founder mutation in Chinese patients differs from the one seen in European patients. Moreover, patients homozygous for the c.545A>G mutation were clinically asymptomatic, a less severe phenotype than in compound heterozygous patients with the c.545A>G mutation. The 13 novel mutations of FKRP significantly expanded the mutation spectrum of MDC1C and LGMD2I, and the different founder mutations indicate the ethnic difference in FKRP mutations.

  2. 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.

  3. 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.

  4. An ancient DNA test of a founder effect in Native American ABO blood group frequencies.

    PubMed

    Halverson, Melissa S; Bolnick, Deborah A

    2008-11-01

    Anthropologists have assumed that reduced genetic diversity in extant Native Americans is due to a founder effect that occurred during the initial peopling of the Americas. However, low diversity could also be the result of subsequent historical events, such as the population decline following European contact. In this study, we show that autosomal DNA from ancient Native American skeletal remains can be used to investigate the low level of ABO blood group diversity in the Americas. Extant Native Americans exhibit a high frequency of blood type O, which may reflect a founder effect, genetic drift associated with the historical population decline, or natural selection in response to the smallpox epidemics that occurred following European contact. To help distinguish between these possibilities, we determined the ABO genotypes of 15 precontact individuals from eastern North America. The precontact ABO frequencies were not significantly different from those observed in extant Native Americans from the same region, but they did differ significantly from the ABO frequencies in extant Siberian populations. Studies of other precontact populations are needed to better test the three hypotheses for low ABO blood group diversity in the Americas, but our findings are most consistent with the hypothesis of a founder effect during the initial settlement of this continent.

  5. 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

    ... Investment Act, Conflicts of Interest Notice is hereby given that Founders Equity SBIC I, L.P., 711 Fifth... exemption under Section 312 of the Act and Section 107.730, Financings Which Constitute Conflicts...

  6. 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

  7. Expression-Guided In Silico Evaluation of Candidate Cis Regulatory Codes for Drosophila Muscle Founder Cells

    PubMed Central

    Gisselbrecht, Stephen S; He, Fangxue Sherry; Estrada, Beatriz; Michelson, Alan M; Bulyk, Martha L

    2006-01-01

    While combinatorial models of transcriptional regulation can be inferred for metazoan systems from a priori biological knowledge, validation requires extensive and time-consuming experimental work. Thus, there is a need for computational methods that can evaluate hypothesized cis regulatory codes before the difficult task of experimental verification is undertaken. We have developed a novel computational framework (termed “CodeFinder”) that integrates transcription factor binding site and gene expression information to evaluate whether a hypothesized transcriptional regulatory model (TRM; i.e., a set of co-regulating transcription factors) is likely to target a given set of co-expressed genes. Our basic approach is to simultaneously predict cis regulatory modules (CRMs) associated with a given gene set and quantify the enrichment for combinatorial subsets of transcription factor binding site motifs comprising the hypothesized TRM within these predicted CRMs. As a model system, we have examined a TRM experimentally demonstrated to drive the expression of two genes in a sub-population of cells in the developing Drosophila mesoderm, the somatic muscle founder cells. This TRM was previously hypothesized to be a general mode of regulation for genes expressed in this cell population. In contrast, the present analyses suggest that a modified form of this cis regulatory code applies to only a subset of founder cell genes, those whose gene expression responds to specific genetic perturbations in a similar manner to the gene on which the original model was based. We have confirmed this hypothesis by experimentally discovering six (out of 12 tested) new CRMs driving expression in the embryonic mesoderm, four of which drive expression in founder cells. PMID:16733548

  8. Tracking HCV protease population diversity during transmission and susceptibility of founder populations to antiviral therapy

    PubMed Central

    Khera, Tanvi; Todt, Daniel; Vercauteren, Koen; McClure, C. Patrick; Verhoye, Lieven; Farhoudi, Ali; Bhuju, Sabin; Geffers, Robert; Baumert, Thomas F.; Steinmann, Eike; Meuleman, Philip; Pietschmann, Thomas; Brown, Richard J.P.

    2017-01-01

    Due to the highly restricted species-tropism of Hepatitis C virus (HCV) a limited number of animal models exist for pre-clinical evaluation of vaccines and antiviral compounds. The human-liver chimeric mouse model allows heterologous challenge with clinically relevant strains derived from patients. However, to date, the transmission and longitudinal evolution of founder viral populations in this model have not been characterized in-depth using state-of-the-art sequencing technologies. Focusing on NS3 protease encoding region of the viral genome, mutant spectra in a donor inoculum and individual recipient mice were determined via Illumina sequencing and compared, to determine the effects of transmission on founder viral population complexity. In all transmissions, a genetic bottleneck was observed, although diverse viral populations were transmitted in each case. A low frequency cloud of mutations (<1%) was detectable in the donor inoculum and recipient mice, with single nucleotide variants (SNVs) > 1% restricted to a subset of nucleotides. The population of SNVs >1% was reduced upon transmission while the low frequency SNV cloud remained stable. Fixation of multiple identical synonymous substitutions was apparent in independent transmissions, and no evidence for reversion of T-cell epitopes was observed. In addition, susceptibility of founder populations to antiviral therapy was assessed. Animals were treated with protease inhibitor (PI) monotherapy to track resistance associated substitution (RAS) emergence. Longitudinal analyses revealed a decline in population diversity under therapy, with no detectable RAS >1% prior to therapy commencement. Despite inoculation from a common source and identical therapeutic regimens, unique RAS emergence profiles were identified in different hosts prior to and during therapeutic failure, with complex mutational signatures at protease residues 155, 156 and 168 detected. Together these analyses track viral population complexity at

  9. 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

  10. Bottlenecks in HIV-1 transmission: insights from the study of founder viruses.

    PubMed

    Joseph, Sarah B; Swanstrom, Ronald; Kashuba, Angela D M; Cohen, Myron S

    2015-07-01

    HIV-1 infection typically results from the transmission of a single viral variant, the transmitted/founder (T/F) virus. Studies of these HIV-1 variants provide critical information about the transmission bottlenecks and the selective pressures acting on the virus in the transmission fluid and in the recipient tissues. These studies reveal that T/F virus phenotypes are shaped by stochastic and selective forces that restrict transmission and may be targets for prevention strategies. In this Review, we highlight how studies of T/F viruses contribute to a better understanding of the biology of HIV-1 transmission and discuss how these findings affect HIV-1 prevention strategies.

  11. 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.

  12. Relative resistance of HIV-1 founder viruses to control by interferon-alpha

    PubMed Central

    2013-01-01

    Background Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. Results The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFNα2 (22 U/ml) was lower than that for IFNβ (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFNα2 and IFNβ, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFNα than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. Conclusions The establishment of systemic HIV-1 infection by

  13. 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

  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.

  15. Cytokinins act directly on lateral root founder cells to inhibit root initiation.

    PubMed

    Laplaze, Laurent; Benkova, Eva; Casimiro, Ilda; Maes, Lies; Vanneste, Steffen; Swarup, Ranjan; Weijers, Dolf; Calvo, Vanessa; Parizot, Boris; Herrera-Rodriguez, Maria Begoña; Offringa, Remko; Graham, Neil; Doumas, Patrick; Friml, Jiri; Bogusz, Didier; Beeckman, Tom; Bennett, Malcolm

    2007-12-01

    In Arabidopsis thaliana, lateral roots are formed from root pericycle cells adjacent to the xylem poles. Lateral root development is regulated antagonistically by the plant hormones auxin and cytokinin. While a great deal is known about how auxin promotes lateral root development, the mechanism of cytokinin repression is still unclear. Elevating cytokinin levels was observed to disrupt lateral root initiation and the regular pattern of divisions that characterizes lateral root development in Arabidopsis. To identify the stage of lateral root development that is sensitive to cytokinins, we targeted the expression of the Agrobacterium tumefaciens cytokinin biosynthesis enzyme isopentenyltransferase to either xylem-pole pericycle cells or young lateral root primordia using GAL4-GFP enhancer trap lines. Transactivation experiments revealed that xylem-pole pericycle cells are sensitive to cytokinins, whereas young lateral root primordia are not. This effect is physiologically significant because transactivation of the Arabidopsis cytokinin degrading enzyme cytokinin oxidase 1 in lateral root founder cells results in increased lateral root formation. We observed that cytokinins perturb the expression of PIN genes in lateral root founder cells and prevent the formation of an auxin gradient that is required to pattern lateral root primordia.

  16. A shared haplotype indicates a founder event in Unverricht-Lundborg disease patients from Serbia.

    PubMed

    Kecmanović, Miljana; Ristić, Aleksandar J; Ercegovac, Marko; Keckarević-Marković, Milica; Keckarević, Dušan; Sokić, Dragoslav; Romac, Stanka

    2014-02-01

    Unverricht-Lundborg disease (ULD) is an autosomal recessive disorder caused by dodecamer repeat expansion in the promoter region of the cystatin B (CSTB) gene in approximately 90% of the disease alleles worldwide. This study presents results of genetic findings in four Serbian unrelated patients with clinical and molecular diagnosis of ULD. Using newly established PCR protocol with betaine, we detected a homozygous expansion of dodecamer repeats in the CSTB gene in four patients with clinical diagnosis of ULD. Our results are in agreement with previous studies showing that dodecamer repeats expansion is the most common mutation associated with ULD. Haplotype analysis of eight unrelated ULD chromosomes was performed using seven markers flanking CSTB gene and one intragenic variant. We demonstrated the existence of a founder effect, strongly supported by LD calculations. Size of the minimal common haplotype implies that the most recent common ancestor of the Serbian ULD patients lived about 110 generations ago. We showed that Serbian ULD patients share the same common ancestor with patients from Baltic countries and North Africa. In the light of our data, we proposed extended minimal common haplotype, which could be considered as initial haplotype of the founder event common for Serbian, Baltic, and North African ULD patients.

  17. PRIMAL: Fast and accurate pedigree-based imputation from sequence data in a founder population.

    PubMed

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

    2015-03-01

    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.

  18. [Max Josef von Pettenkofer--founder of modern hygiene (1818-1901)].

    PubMed

    Paunović, Katarina; Maksimović, Milos; Davidović, Dragana; Milenković, Sanja; Slepcević, Vesna

    2005-01-01

    Max Josef von Pettenkofer was one of the leading personalities in the world of medicine in the 19th century. He was the founder of the modern science of hygiene. In his experimental work, he was involved in the research of problems dealing with the relationship between human beings and the environment, including such topics as soil and air pollution, water supply, sewage water management, room ventilation and heating, as well as the function of clothing and the cleanliness of homes and streets. Pettenkofer also studied the onset, the course, and the consequences of infectious diseases, such as cholera and typhus. He realised the great economic value of public health and emphasised that personal preventive measures should be supplemented with the improvement of factors in communal and work environments. His efforts lead to hygiene becoming a part of medical studies in 1865. The Institute for Hygiene at the School of Medicine in Munich was established in 1879. It was constructed according to his drawings and was considered to be the most modern institute for hygiene in the world. Since hygiene was a subject on the school curriculum in the German Empire in 1882, Pettenkofer became the Chairman of Hygiene in Berlin in 1885. Research institutions established by Pettenkofer and the fact that many of his students became professors of hygiene speak about the importance of his work. One of his students was professor Milan Jovanović Batut, founder of the Institute for Hygiene at the School of Medicine in Belgrade.

  19. No common founder for C9orf72 expansion mutation in Sweden.

    PubMed

    Chiang, Huei-Hsin; Forsell, Charlotte; Lindström, Anna-Karin; Lilius, Lena; Thonberg, Håkan; Nennesmo, Inger; Graff, Caroline

    2017-02-01

    Hexanucleotide expansion mutations in the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic cause for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). SNP haplotype analyses have suggested that all C9orf72 expansion mutations originate from a common founder. However, not all C9orf72 expansion mutation carriers have the same haplotype. To investigate if the C9orf72 expansion mutation carriers in Sweden share a common founder, we have genotyped SNPs flanking the C9orf72 expansion mutation in cases with FTD, FTD-ALS or ALS to perform haplotype analysis. We have genotyped 57 SNPs in 232 cases of which 45 carried the C9orf72 expansion mutation. Two risk haplotypes consisting of 31 SNPs, spanning 131 kbp, were found to be significantly associated with the mutation. In summary, haplotype analysis on Swedish C9orf72 expansion mutation carriers indicates that the C9orf72 expansion mutation arose on at least two risk haplotypes.

  20. Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world.

    PubMed

    Lund, A; Udd, B; Juvonen, V; Andersen, P M; Cederquist, K; Davis, M; Gellera, C; Kölmel, C; Ronnevi, L O; Sperfeld, A D; Sörensen, S A; Tranebjaerg, L; Van Maldergem, L; Watanabe, M; Weber, M; Yeung, L; Savontaus, M L

    2001-06-01

    SBMA (spinal and bulbar muscular atrophy), also called Kennedy disease, is an X-chromosomal recessive adult-onset neurodegenerative disorder caused by death of the spinal and bulbar motor neurones and dorsal root ganglia. Patients may also show signs of partial androgen insensitivity. SBMA is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene on the X-chromosome. Our previous study suggested that all the Nordic patients with SBMA originated from an ancient Nordic founder mutation, but the new intragenic SNP marker ARd12 revealed that the Danish patients derive their disease chromosome from another ancestor. In search of relationships between patients from different countries, we haplotyped altogether 123 SBMA families from different parts of the world for two intragenic markers and 16 microsatellites spanning 25 cM around the AR gene. The fact that different SBMA founder haplotypes were found in patients from around the world implies that the CAG repeat expansion mutation has not been a unique event. No expansion-prone haplotype could be detected. Trinucleotide diseases often show correlation between the repeat length and the severity and earlier onset of the disease. The longer the repeat, the more severe the symptoms are and the onset of the disease is earlier. A negative correlation between the CAG repeat length and the age of onset was found in the 95 SBMA patients with defined ages at onset.

  1. Founder effect in spinal and bulbar muscular atrophy (SBMA) in Scandinavia.

    PubMed

    Lund, A; Udd, B; Juvonen, V; Andersen, P M; Cederquist, K; Ronnevi, L O; Sistonen, P; Sörensen, S A; Tranebjaerg, L; Wallgren-Pettersson, C; Savontaus, M L

    2000-08-01

    We haplotyped 13 Finnish, 10 Swedish, 12 Danish and 2 Norwegian SBMA (spinal and bulbar muscular atrophy, Kennedy disease) families with a total of 45 patients and 7 carriers for 17 microsatellite markers spanning a 25.2 cM region around the androgen receptor gene on chromosome Xq11-q12 in search of a genetic founder effect. In addition, the haplotypes of 50 Finnish, 20 Danish and 22 Swedish control males were examined. All the Scandinavian SBMA families shared the same 18 repeat allele for the intragenic GGC repeat, which was present in only 24% of the controls. Linkage disequilibrium was also seen for the closest microsatellite markers. In addition, extended haplotypes of the Finnish, Swedish and Danish SBMA families revealed country-specific common founder haplotypes, which over time became gradually shortened by recombinations. No common haplotype was found among the controls. The data suggest that the SBMA mutation was introduced into western Finland 20 generations ago. Haplotype analysis implies a common ancestor for the majority of Scandinavian SBMA patients.

  2. 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

  3. 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.

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

    PubMed

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

    2014-12-22

    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.

  5. 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

  6. High relative frequency of SCA1 in Poland reflecting a potential founder effect.

    PubMed

    Krysa, Wioletta; Sulek, Anna; Rakowicz, Maria; Szirkowiec, Walentyna; Zaremba, Jacek

    2016-08-01

    Spinocerebellar ataxias (SCAs) have irregular distributions worldwide. SCA1 is the most frequent in Poland, and no cases of SCA3 of Polish origin has yet been identified. In view of such patterns of SCAs occurrence, the relative frequency, geographical distribution and a possible founder effect of SCA1 were investigated. DNA samples of 134 probands with SCA1 and 228 controls were analysed. The genotyping of four markers, D6S89, D6S109, D6S274, D6S288, around the ATXN1 gene (SCA1) and sequencing of the selected variant of D6S89 were performed. The relative frequency of SCA1 was 68 %. The studied SCA1 pedigrees were irregularly distributed, with the highest concentration in Central Poland. Haplotyping revealed the association of ATXN1 gene mutation with a 197-bp variant of D6S89 marker (63 % of probands) and with a 184-bp variant of DS6274 (50.7 % of probands). Out of 61 SCA1 probands from Mazowieckie, 41 carried the same 197-bp variant. SCA1 relative frequency in Poland shows the highest value compared with the data from other countries worldwide. Due to the association with the mutation obtained for the investigated markers and the SCA1 pedigrees concentration in Central Poland, we hypothesise that it represents a potential founder effect.

  7. 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

  8. 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.

  9. Tracking HCV protease population diversity during transmission and susceptibility of founder populations to antiviral therapy.

    PubMed

    Khera, Tanvi; Todt, Daniel; Vercauteren, Koen; McClure, C Patrick; Verhoye, Lieven; Farhoudi, Ali; Bhuju, Sabin; Geffers, Robert; Baumert, Thomas F; Steinmann, Eike; Meuleman, Philip; Pietschmann, Thomas; Brown, Richard J P

    2017-03-01

    Due to the highly restricted species-tropism of Hepatitis C virus (HCV) a limited number of animal models exist for pre-clinical evaluation of vaccines and antiviral compounds. The human-liver chimeric mouse model allows heterologous challenge with clinically relevant strains derived from patients. However, to date, the transmission and longitudinal evolution of founder viral populations in this model have not been characterized in-depth using state-of-the-art sequencing technologies. Focusing on NS3 protease encoding region of the viral genome, mutant spectra in a donor inoculum and individual recipient mice were determined via Illumina sequencing and compared, to determine the effects of transmission on founder viral population complexity. In all transmissions, a genetic bottleneck was observed, although diverse viral populations were transmitted in each case. A low frequency cloud of mutations (<1%) was detectable in the donor inoculum and recipient mice, with single nucleotide variants (SNVs) > 1% restricted to a subset of nucleotides. The population of SNVs >1% was reduced upon transmission while the low frequency SNV cloud remained stable. Fixation of multiple identical synonymous substitutions was apparent in independent transmissions, and no evidence for reversion of T-cell epitopes was observed. In addition, susceptibility of founder populations to antiviral therapy was assessed. Animals were treated with protease inhibitor (PI) monotherapy to track resistance associated substitution (RAS) emergence. Longitudinal analyses revealed a decline in population diversity under therapy, with no detectable RAS >1% prior to therapy commencement. Despite inoculation from a common source and identical therapeutic regimens, unique RAS emergence profiles were identified in different hosts prior to and during therapeutic failure, with complex mutational signatures at protease residues 155, 156 and 168 detected. Together these analyses track viral population complexity

  10. Founder effect in beta-thalassaemia in Portneuf, Québec.

    PubMed

    De Braekeleer, M; Dao, T N

    1993-08-01

    The genealogies of seven individuals with beta-thalassaemia minor carrying the (beta+IVS-1, nt110) mutation were reconstructed to determine the origin of the mutation in the French Canadian population of Portneuf County. A set of 55 ancestors common to all seven carriers was defined. These founders included 38 born in Europe of whom 34 came from 13 different regions of France and in particular from Languedoc (2 ancestors), a French province along the Mediterranean sea in which the mutation is still present. Descendants of these two individuals settled in Portneuf County where the gene frequency increased due to a high level of endogamy. However, present results cannot exclude a possibility that the (beta+IVS-1, nt110) mutation was introduced into the French Canadian population by settlers originating from a non-malarial region of France. The beta-thalassaemia gene has since spread from Portneuf County over the last century.

  11. 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.

  12. 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.

  13. An intriguing "silent" mutation and a founder effect in antiquitin (ALDH7A1).

    PubMed

    Salomons, Gajja S; Bok, Levinus A; Struys, Eduard A; Pope, Lorna Landegge; Darmin, Patricia S; Mills, Philippa B; Clayton, Peter T; Willemsen, Michèl A; Jakobs, Cornelis

    2007-10-01

    Recently, alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was shown to cause pyridoxine-dependent epilepsy in a considerable number of patients. alpha-AASA dehydrogenase deficiency is an autosomal recessive disorder characterized by a neonatal-onset epileptic encephalopathy in which seizures are resistant to antiepileptic drugs but respond immediately to the administration of pyridoxine (OMIM 266100). Increased plasma and urinary levels of alpha-AASA are associated with pathogenic mutations in the alpha-AASA dehydrogenase (ALDH7A1/antiquitin) gene. Here, we report an intriguing "silent" mutation in ALDH7A1, a novel missense mutation and a founder mutation in a Dutch cohort (10 patients) with alpha-AASA dehydrogenase deficiency.

  14. 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

  15. The first independent pharmacognosy institute in the world and its founder Julije Domac (1853-1928).

    PubMed

    Inić, S; Kujundzić, N

    2011-09-01

    The aim of this article is to describe the foundation and development of the first distinct Institute of Pharmacognosy in the world and to provide a biography of its founder Julije Domac. The Institute was founded in 1896 as a separate institution at the University of Zagreb, Croatia, part of the Austro-Hungarian Empire at the time. In other European university centers, pharmacognosy institutes were founded together with pharmacology, botany, pharmaceutical or general chemistry. Julije Domac (1853-1928) graduated pharmacy from the University of Vienna (1874) and received his Ph.D. from the University of Graz (1880) with a paper elucidating the structure of hexene and mannitol obtained from manna. He lectured pharmacognosy at the University of Zagreb (1887-1924), wrote chemistry and pharmacognosy textbooks, and co-wrote the Croatian-Slavonian Pharmacopoeia.

  16. 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...

  17. Characterization of an Italian Founder Mutation in the RING-Finger Domain of BRCA1

    PubMed Central

    Colombo, Mara; Congregati, Caterina; Sarkar, Mohosin; Magliery, Thomas J.; Ripamonti, Carla B.; Foglia, Claudia; Peissel, Bernard; Zaffaroni, Daniela; Manoukian, Siranoush; Tondini, Carlo; Barile, Monica; Pensotti, Valeria; Bernard, Loris

    2014-01-01

    The identification of founder mutations in cancer predisposing genes is important to improve risk assessment in geographically defined populations, since it may provide specific targets resulting in cost-effective genetic testing. Here, we report the characterization of the BRCA1 c.190T>C (p.Cys64Arg) mutation, mapped to the RING-finger domain coding region, that we detected in 43 hereditary breast/ovarian cancer (HBOC) families, for the large part originating from the province of Bergamo (Northern Italy). Haplotype analysis was performed in 21 families, and led to the identification of a shared haplotype extending over three BRCA1-associated marker loci (0.4 cM). Using the DMLE+2.2 software program and regional population demographic data, we were able to estimate the age of the mutation to vary between 3,100 and 3,350 years old. Functional characterization of the mutation was carried out at both transcript and protein level. Reverse transcriptase-PCR analysis on lymphoblastoid cells revealed expression of full length mRNA from the mutant allele. A green fluorescent protein (GFP)-fragment reassembly assay showed that the p.Cys64Arg substitution prevents the binding of the BRCA1 protein to the interacting protein BARD1, in a similar way as proven deleterious mutations in the RING-domain. Overall, 55 of 83 (66%) female mutation carriers had a diagnosis of breast and/or ovarian cancer. Our observations indicate that the BRCA1 c.190T>C is a pathogenic founder mutation present in the Italian population. Further analyses will evaluate whether screening for this mutation can be suggested as an effective strategy for the rapid identification of at-risk individuals in the Bergamo area. PMID:24516540

  18. Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population

    PubMed Central

    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

    2014-01-01

    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

  19. A personalised approach to prostate cancer screening based on genotyping of risk founder alleles

    PubMed Central

    Cybulski, C; Wokołorczyk, D; Kluźniak, W; Kashyap, A; Gołąb, A; Słojewski, M; Sikorski, A; Puszyński, M; Soczawa, M; Borkowski, T; Borkowski, A; Antczak, A; Przybyła, J; Sosnowski, M; Małkiewicz, B; Zdrojowy, R; Domagała, P; Piotrowski, K; Menkiszak, J; Krzystolik, K; Gronwald, J; Jakubowska, A; Górski, B; Dębniak, T; Masojć, B; Huzarski, T; Muir, K R; Lophatananon, A; Lubiński, J; Narod, S A

    2013-01-01

    Background: To evaluate whether genotyping for 18 prostate cancer founder variants is helpful in identifying high-risk individuals and for determining optimal screening regimens. Methods: A serum PSA level was measured and a digital rectal examination (DRE) was performed on 2907 unaffected men aged 40–90. Three hundred and twenty-three men with an elevated PSA (⩾4 ng ml−1) or an abnormal DRE underwent a prostate biopsy. All men were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA and C61G), for four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395 and I157T), for one allele in NBS1 (657del5), for one allele in HOXB13 (G84E), and for nine low-risk single-nucleotide polymorphisms (SNPs). Results: On the basis of an elevated PSA or an abnormal DRE, prostate cancer was diagnosed in 135 of 2907 men (4.6%). In men with a CHEK2 missense mutation I157T, the cancer detection rate among men with an elevated PSA or an abnormal DRE was much higher (10.2%, P=0.0008). The cancer detection rate rose with the number of SNP risk genotypes observed from 1.2% for men with no variant to 8.6% for men who carried six or more variants (P=0.04). No single variant was helpful on its own in predicting the presence of prostate cancer, however, the combination of all rare mutations and SNPs improved predictive power (area under the curve=0.59; P=0.03). Conclusion: These results suggest that testing for germline CHEK2 mutations improves the ability to predict the presence of prostate cancer in screened men, however, the clinical utility of incorporating DNA variants in the screening process is marginal. PMID:23722471

  20. Congenital sucrase–isomaltase deficiency: identification of a common Inuit founder mutation

    PubMed Central

    Marcadier, Julien L.; Boland, Margaret; Scott, C. Ronald; Issa, Kheirie; Wu, Zaining; McIntyre, Adam D.; Hegele, Robert A.; Geraghty, Michael T.; Lines, Matthew A.

    2015-01-01

    Background: Congenital sucrase–isomaltase deficiency is a rare hereditary cause of chronic diarrhea in children. People with this condition lack the intestinal brush-border enzyme required for digestion of di- and oligosaccharides, including sucrose and isomaltose, leading to malabsorption. Although the condition is known to be highly prevalent (about 5%–10%) in several Inuit populations, the genetic basis for this has not been described. We sought to identify a common mutation for congenital sucrase–isomaltase deficiency in the Inuit population. Methods: We sequenced the sucrase–isomaltase gene, SI, in a single Inuit proband with congenital sucrase–isomaltase deficiency who had severe fermentative diarrhea and failure to thrive. We then genotyped a further 128 anonymized Inuit controls from a variety of locales in the Canadian Arctic to assess for a possible founder effect. Results: In the proband, we identified a novel, homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), predicted to result in complete absence of a functional protein product. This change was very common among the Inuit controls, with an observed allele frequency of 17.2% (95% confidence interval [CI] 12.6%–21.8%). The predicted Hardy–Weinberg prevalence of congenital sucrase–isomaltase deficiency in Inuit people, based on this single founder allele, is 3.0% (95% CI 1.4%–4.5%), which is comparable with previous estimates. Interpretation: We found a common mutation, SI c.273_274delAG, to be responsible for the high prevalence of congenital sucrase–isomaltase deficiency among Inuit people. Targeted mutation testing for this allele should afford a simple and minimally invasive means of diagnosing this condition in Inuit patients with chronic diarrhea. PMID:25452324

  1. 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.

  2. Patterns in avian malaria at founder and source populations of an endemic New Zealand passerine.

    PubMed

    Baillie, Shauna M; Gudex-Cross, David; Barraclough, Rosemary K; Blanchard, Wade; Brunton, Dianne H

    2012-11-01

    Significant progress in our understanding of disease transmission in the wild can be made by examining variation in host-parasite-vector interactions after founder events of the host. This study is the first to document patterns in avian malaria, Plasmodium spp., infecting an endemic New Zealand passerine, Anthornis melanura, at multiple-host subpopulations simultaneously. We assess the Beaudoin hypothesis of bimodal seasonality and use AIC model selection to determine host factors associated with disease prevalence. We had the rare opportunity to test the enemy release hypothesis (ERH) after a recent colonisation event of the bellbird host. Four Plasmodium species were found to infect bellbirds. Temporal patterns of three exotic parasite lineages, including GRW06 Plasmodium (Huffia) elongatum, SYAT05 Plasmodium (Novyella) vaughani and a Plasmodium (Haemamoeba) relictum, were sporadic with low prevalence year round. The fourth species was an endemic parasite, an unresolved Plasmodium (Novyella) sp. here called ANME01, which exhibited a strong winter peak at the source subpopulations possibly indicating greater immune stressors at the densely populated source site. At the colonies, we observed bimodal seasonality in the prevalence of ANME01 with autumn and spring peaks. These infection peaks were male-biased, and the amplitude of sex bias was more pronounced at the newer colony perhaps due to increased seasonal competition resulting from territory instability. We observed a decrease in parasite species diversity and increase in body condition from source to founder sites, but statistical differences in the direct relationship between body condition and malaria prevalence between source and colony were weak and significant only during winter. Though our data did not strongly support the ERH, we highlight the benefits of 'conspecific release' associated with decreased population density and food competition. Our findings contribute to the identification of ecological

  3. 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.

  4. 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…

  5. 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…

  6. Local and regional founder effects in lake zooplankton persist after thousands of years despite high dispersal potential.

    PubMed

    Ventura, M; Petrusek, A; Miró, A; Hamrová, E; Buñay, D; De Meester, L; Mergeay, J

    2014-03-01

    We reconstructed the genetic structure of a planktonic crustacean Daphnia longispina living in high mountain lakes and ponds in the Pyrenees to investigate whether it was shaped by persistent founder effects originating shortly after the last glacial maximum or by ongoing dispersal and effective migration (gene flow). We found that the genetic structure can largely be explained by a single colonization event following gradual deglaciation of the Pyrenees ~10 000-15 000 years ago. Nuclear genetic diversity declined steeply from southeast to northwest, suggestive of serial colonization of available habitats with advancing deglaciation. The spatial genetic structure suggests that founder effects were major determinants of the present-day diversity, both at the catchment level and at the level of individual water bodies, further supporting extremely low effective migration rates. This study reveals a prime example of a founder effect that is both long lasting and maintained at small spatial scales. Our data suggest a process of isolation by colonization as a result of strong priority effects and monopolization. We found evidence for the spread of haplotypes with Pyrenean ancestry across the Palaearctic over distances up to 5500 km, although the local genetic structure after colonization was hardly influenced by contemporary dispersal. Finally, our data also suggest that mitochondrial mutation rates in the studied populations were seven times higher than typically assumed. Overall, we show that founder effects can persist for centuries even at small spatial scales at which the potential for dispersal is high.

  7. 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…

  8. Apple founder targets healthcare as NeXT market. Interview by Carolyn Dunbar and Michael L. Laughlin.

    PubMed

    Jobs, S

    1992-12-01

    Cofounder and former chairman of the board of Apple Computer Steven Jobs looks beyond the 1980s image of a petulant, embittered young man, fighting with all who failed to share his vision, and many who did. Today, as a founder, president and chairman of NeXT, Inc., he looks to more high-minded applications of his computer genius.

  9. [Johann Friedrich Dieffenbach (1792-1847) as the founder of plastic surgery. His contribution to maxillofacial surgery].

    PubMed

    Schultheiss, D; Knöner, W; Kramer, F J; Jonas, U

    1998-11-01

    Johann Friedrich Dieffenbach (1792-1847) is generally known as the founder of modern plastic surgery. One focus of his work, apart from the physiology of transplantation and operative techniques, was reconstructive oral and maxillofacial surgery. This special aspect of plastic surgery as well as Dieffenbach's biography is presented in this historic article.

  10. A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families.

    PubMed

    Phelan, Catherine M; Kwan, Elaine; Jack, Elaine; Li, Song; Morgan, Cindy; Aubé, Jennifer; Hanna, Danielle; Narod, Steven A

    2002-11-01

    The 185delAG and 5382insC founder mutations account for the majority of mutations identified in BRCA1 in Ashkenazi Jewish breast and breast-ovarian cancer families. Few non-founder BRCA1 mutations have been identified to date in these families. We initially screened a panel of 245 Ashkenazi Jewish breast-ovarian cancer families with an affected proband and at least one other case of breast or ovarian cancer for founder mutations in BRCA1 and BRCA2. Founder mutations were identified in 85 families (185delAG in 44 families, 5382insC in 16 families, and the BRCA2 6174delT in 25 families). The 160 negative families were then screened for the entire BRCA1 gene by a combination of DGGE and PTT. We identified one novel frameshift mutation in BRCA1 in exon 14 (4572del22) that truncated the protein at codon 1485. The family contained three cases of early-onset ovarian cancer (41 years, 43 years, and 52 years) and one case of breast cancer (at age 54 years subsequent to an ovarian cancer). In addition, three missense variants of unknown significance (exon 11 C3832T (P1238L), exon 15 G4654T (S1512I), and exon 15 G4755A (D1546N)) were found in single families. These missense variants have been previously identified in other families [BIC Database] and are considered to be "unclassified variants, favoring polymorphism." Non-founder BRCA1 mutations are rare in Ashkenazi Jewish breast/ovarian cancer families.

  11. Geochemical evidence for pre- and syn-rifting lithospheric foundering in the East African Rift System

    NASA Astrophysics Data System (ADS)

    Nelson, W. R.; Furman, T.; Elkins-Tanton, L. T.

    2015-12-01

    The East African Rift System (EARS) is the archetypal active continental rift. The rift branches cut through the elevated Ethiopian and Kenyan domes and are accompanied by a >40 Myr volcanic record. This record is often used to understand changing mantle dynamics, but this approach is complicated by the diversity of spatio-temporally constrained, geochemically unique volcanic provinces. Various sources have been invoked to explain the geochemical variability across the EARS (e.g. mantle plume(s), both enriched and depleted mantle, metasomatized or pyroxenitic lithosphere, continental crust). Mantle contributions are often assessed assuming adiabatic melting of mostly peridotitic material due to extension or an upwelling thermal plume. However, metasomatized lithospheric mantle does not behave like fertile or depleted peridotite mantle, so this model must be modified. Metasomatic lithologies (e.g. pyroxenite) are unstable compared to neighboring peridotite and can founder into the underlying asthenosphere via ductile dripping. As such a drip descends, the easily fusible metasomatized lithospheric mantle heats conductively and melts at increasing T and P; the subsequent volcanic products in turn record this drip magmatism. We re-evaluated existing data of major mafic volcanic episodes throughout the EARS to investigate potential evidence for lithospheric drip foundering that may be an essential part of the rifting process. The data demonstrate clearly that lithospheric drip melting played an important role in pre-flood basalt volcanism in Turkana (>35 Ma), high-Ti "mantle plume-derived" flood basalts and picrites (HT2) from NW Ethiopia (~30 Ma), Miocene shield volcanism on the E Ethiopian Plateau and in Turkana (22-26 Ma), and Quaternary volcanism in Virunga (Western Rift) and Chyulu Hills (Eastern Rift). In contrast, there is no evidence for drip melting in "lithosphere-derived" flood basalts (LT) from NW Ethiopia, Miocene volcanism in S Ethiopia, or Quaternary

  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. Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequence.

    PubMed

    Tan-Sindhunata, M Brigita; Mathijssen, Inge B; Smit, Margriet; Baas, Frank; de Vries, Johanna I; van der Voorn, J Patrick; Kluijt, Irma; Hagen, Marleen A; Blom, Eveline W; Sistermans, Erik; Meijers-Heijboer, Hanne; Waisfisz, Quinten; Weiss, Marjan M; Groffen, Alexander J

    2015-09-01

    Fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. FADS can result from mutations in CHRNG, CHRNA1, CHRND, DOK7 and RAPSN; however, these genes only account for a minority of cases. Here we identify MUSK as a novel cause of lethal FADS. Fourteen affected fetuses from a Dutch genetic isolate were traced back to common ancestors 11 generations ago. Homozygosity mapping in two fetuses revealed MUSK as a candidate gene. All tested cases carried an identical homozygous variant c.1724T>C; p.(Ile575Thr) in the intracellular domain of MUSK. The carrier frequency in the genetic isolate was 8%, exclusively found in heterozygous carriers. Consistent with the established role of MUSK as a tyrosine kinase that orchestrates neuromuscular synaptogenesis, the fetal myopathy was accompanied by impaired acetylcholine receptor clustering and reduced tyrosine kinase activity at motor nerve endings. A functional assay in myocytes derived from human fetuses confirmed that the variant blocks MUSK-dependent motor endplate formation. Taken together, the results strongly support a causal role of this founder mutation in MUSK, further expanding the gene set associated with FADS and offering new opportunities for prenatal genetic testing.

  14. Identification of a Dutch founder mutation in MUSK causing fetal akinesia deformation sequence

    PubMed Central

    Tan-Sindhunata, M Brigita; Mathijssen, Inge B; Smit, Margriet; Baas, Frank; de Vries, Johanna I; van der Voorn, J Patrick; Kluijt, Irma; Hagen, Marleen A; Blom, Eveline W; Sistermans, Erik; Meijers-Heijboer, Hanne; Waisfisz, Quinten; Weiss, Marjan M; Groffen, Alexander J

    2015-01-01

    Fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. FADS can result from mutations in CHRNG, CHRNA1, CHRND, DOK7 and RAPSN; however, these genes only account for a minority of cases. Here we identify MUSK as a novel cause of lethal FADS. Fourteen affected fetuses from a Dutch genetic isolate were traced back to common ancestors 11 generations ago. Homozygosity mapping in two fetuses revealed MUSK as a candidate gene. All tested cases carried an identical homozygous variant c.1724T>C; p.(Ile575Thr) in the intracellular domain of MUSK. The carrier frequency in the genetic isolate was 8%, exclusively found in heterozygous carriers. Consistent with the established role of MUSK as a tyrosine kinase that orchestrates neuromuscular synaptogenesis, the fetal myopathy was accompanied by impaired acetylcholine receptor clustering and reduced tyrosine kinase activity at motor nerve endings. A functional assay in myocytes derived from human fetuses confirmed that the variant blocks MUSK-dependent motor endplate formation. Taken together, the results strongly support a causal role of this founder mutation in MUSK, further expanding the gene set associated with FADS and offering new opportunities for prenatal genetic testing. PMID:25537362

  15. 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.

  16. 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.

  17. Rejection of a serial founder effects model of genetic and linguistic coevolution.

    PubMed

    Hunley, Keith; Bowern, Claire; Healy, Meghan

    2012-06-07

    Recent genetic studies attribute the negative correlation between population genetic diversity and distance from Africa to a serial founder effects (SFE) evolutionary process. A recent linguistic study concluded that a similar decay in phoneme inventories in human languages was also the product of the SFE process. However, the SFE process makes additional predictions for patterns of neutral genetic diversity, both within and between groups, that have not yet been tested on phonemic data. In this study, we describe these predictions and test them on linguistic and genetic samples. The linguistic sample consists of 725 widespread languages, which together contain 908 distinct phonemes. The genetic sample consists of 614 autosomal microsatellite loci in 100 widespread populations. All aspects of the genetic pattern are consistent with the predictions of SFE. In contrast, most of the predictions of SFE are violated for the phonemic data. We show that phoneme inventories provide information about recent contacts between languages. However, because phonemes change rapidly, they cannot provide information about more ancient evolutionary processes.

  18. Use of Dried Blood Spots to Elucidate Full-Length Transmitted/Founder HIV-1 Genomes

    PubMed Central

    Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Tully, Damien C.; Ogilvie, Colin B.; Learn, Gerald H.; Allen, Todd M.; Heath, Sonya L.; Goepfert, Paul; Bar, Katharine J.

    2016-01-01

    Background Identification of HIV-1 genomes responsible for establishing clinical infection in newly infected individuals is fundamental to prevention and pathogenesis research. Processing, storage, and transportation of the clinical samples required to perform these virologic assays in resource-limited settings requires challenging venipuncture and cold chain logistics. Here, we validate the use of dried-blood spots (DBS) as a simple and convenient alternative to collecting and storing frozen plasma. Methods We performed parallel nucleic acid extraction, single genome amplification (SGA), next generation sequencing (NGS), and phylogenetic analyses on plasma and DBS. Results We demonstrated the capacity to extract viral RNA from DBS and perform SGA to infer the complete nucleotide sequence of the transmitted/founder (TF) HIV-1 envelope gene and full-length genome in two acutely infected individuals. Using both SGA and NGS methodologies, we showed that sequences generated from DBS and plasma display comparable phylogenetic patterns in both acute and chronic infection. SGA was successful on samples with a range of plasma viremia, including samples as low as 1,700 copies/ml and an estimated ∼50 viral copies per blood spot. Further, we demonstrated reproducible efficiency in gp160 env sequencing in DBS stored at ambient temperature for up to three weeks or at -20°C for up to five months. Conclusions These findings support the use of DBS as a practical and cost-effective alternative to frozen plasma for clinical trials and translational research conducted in resource-limited settings. PMID:27819061

  19. Cytokinin-mediated cell cycling arrest of pericycle founder cells in lateral root initiation of Arabidopsis.

    PubMed

    Li, Xiang; Mo, Xiaorong; Shou, Huixia; Wu, Ping

    2006-08-01

    In Arabidopsis, lateral root formation is a post-embryonic developmental event, which is regulated by hormones and environmental signals. In this study, via analyzing the expression of cyclin genes during lateral root (LR) formation, we report that cytokinins (CTKs) inhibit the initiation of LR through blocking the pericycle founder cells cycling at the G(2) to M transition phase, while the promotion by CTK of LR elongation is due to the stimulation of the G(1) to S transition. No significant difference was detected in the inhibitory effect of CTK on LR formation between wild-type plants and mutants defective in auxin response or transport. In addition, exogenously applied auxin at different concentrations could not rescue the CTK-mediated inhibition of LR initiation. Our data suggest that CTK and auxin might control LR initiation through two separate signaling pathways in Arabidopsis. The CTK-mediated repression of LR initiation is transmitted through the two-component signal system and mediated by the receptor CRE1.

  20. Shipwrecks and founder effects: divergent demographic histories reflected in Caribbean mtDNA.

    PubMed

    Salas, Antonio; Richards, Martin; Lareu, María-Victoria; Sobrino, Beatriz; Silva, Sandra; Matamoros, Mireya; Macaulay, Vincent; Carracedo, Angel

    2005-12-01

    During the period of the Atlantic slave trade (15th-19th centuries), millions of people were forced to move from Africa to many American destinations, changing dramatically the human landscape of the Americas. Here, we analyze mitochondrial DNA from two different American populations with African ancestry, with hitherto unknown European and Native American components. On the basis of historical records, African-Americans from Chocó (Colombia) and the Garífunas (or "Black Carib") of Honduras are likely to have had very different demographic histories, with a significant founder effect in the formation of the latter. Both the common features and differences are reflected in their mtDNA composition. Both show a minor component (approximately 16%) from Native Central/South Americans and a larger component (approximately 84%) from sub-Saharan Africans. The latter component is very diverse in the African-Americans from Chocó, similar to that of sub-Saharan Africans, but much less so in the Garífunas, with several mtDNA types elevated to high frequency, suggesting the action of genetic drift.

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

    PubMed

    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; Kamanga, Gift; Louder, Mark K; Tran, Lillian M; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, M Gordon; 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

    2013-04-25

    Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage 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 determine 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 by vaccination.

  2. C329X in KRIT1 is a founder mutation among CCM patients in Sardinia.

    PubMed

    Cau, Milena; Loi, Mario; Melis, Maurizio; Congiu, Rita; Loi, Alberto; Meloni, Cristiana; Serrenti, Marianna; Addis, Maria; Melis, Maria Antonietta

    2009-01-01

    Cerebral cavernous malformations (CCMs) are CNS vascular anomalies associated with seizures, headaches and hemorrhagic strokes and represent 10-20% of cerebral lesions. CCM is present in 0.1-0.5 of the population. This disorder most often occurs sporadically but may also be familial. Familial cases are inherited as a dominant trait with incomplete penetrance and are estimated to account for KRIT1 10-40% of the patients. The identification of the genes involved in such disorders allows to characterize carriers of the mutations without clear symptoms. The first gene involved in CCM1 is KRIT1. In addition to two other genes have been described: MGC4607 (CCM2) and PDCD10 (CCM3). We selected 13 patients belonging to seven Sardinian families on the basis of clinical symptoms and Magnetic Resonance results. In MGC4607 gene an undescribed exon five deletion likely producing a truncated protein was identified in one family. In two patients with clear phenotype and in three asymptomatic relatives a 4 bp deletion in exon 9 of KRIT1 gene, leading to a premature stop codon, was detected. A unique nonsense mutation (C329X) has been found in seven patients and two asymptomatic subjects belonging to four unrelated families. Haplotype analysis revealed a common origin of this mutation. These data suggest a "founder effect" in Sardinia for the C329X mutation, similar to other mutations described in different populations.

  3. Sergei Winogradsky: a founder of modern microbiology and the first microbial ecologist.

    PubMed

    Dworkin, Martin

    2012-03-01

    Sergei Winogradsky, was born in Russia in 1856 and was to become a founder of modern microbiology. After his Master's degree work on the nutrition and growth physiology of the yeast Mycoderma vini at the University of St. Petersburg, he joined the laboratory of Anton DeBary in Strassburg. There he carried out his studies on the sulfur-oxidizing bacterium Beggiatoa which resulted in his formulation of the theory of chemolithotrophy. He then joined the Swiss Polytechnic Institute in Zurich where he did his monumental work on bacterial nitrification. He isolated the first pure cultures of the nitrifying bacteria and confirmed that they carried out the separate steps of the conversion of ammonia to nitrite and of nitrite to nitrate. This led directly to the concept of the cycles of sulfur and nitrogen in Nature. He returned to Russia and there was the first to isolate a free-living dinitrogen-fixing bacterium. In the flush of success, he retired from science and spent 15 years on his familial estate in the Ukraine. The Russian revolution forced him to flee Russia. He joined the Pasteur Institute in Paris where he spent his remaining 24 years initiating and developing the field of microbial ecology. He died in 1953.

  4. A prevalent mutation with founder effect in xeroderma pigmentosum group C from north Africa.

    PubMed

    Soufir, Nadem; Ged, Cecile; Bourillon, Agnes; Austerlitz, Frederic; Chemin, Cécile; Stary, Anne; Armier, Jacques; Pham, Daniele; Khadir, Khadija; Roume, Joelle; Hadj-Rabia, Smail; Bouadjar, Bakar; Taieb, Alain; de Verneuil, Hubert; Benchiki, Hakima; Grandchamp, Bernard; Sarasin, Alain

    2010-06-01

    Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that is associated with an inherited defect of the nucleotide excision repair pathway (NER). In this study, we investigated the involvement of XP genes in 86 XP patients belonging to 66 unrelated families, most of them consanguineous and originating from Maghreb. Sequencing analysis was performed either directly (44 probands) or after having previously characterized the involved XP gene by complementation assay (22 families). XPC and XPA mutations were respectively present in 56/66 and 8/66 probands. Strikingly, we identified the same homozygous frameshift mutation c.1643_1644delTG (p.Val548AlafsX25) in 87% of XP-C patients. Haplotype analysis showed a common founder effect for this mutation in the Mediterranean region, with an estimated age of 50 generations or 1,250 years. Among 7/8 XP-A patients, we found the previously reported nonsense homozygous XPA mutation (p.Arg228X). Six mutations--to our knowledge previously unreported--(five in XPC, one in XPA) were also identified. In conclusion, XPC appears to be the major disease-causing gene concerning xeroderma pigmentosum in North Africa. As the (p.Val548AlafsX25) XPC mutation is responsible for a huge proportion of XP cases, our data imply an obvious simplification of XP molecular diagnosis, at least in North Africa.

  5. [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.

  6. Arsov Dimitar, founder of the modern internal medicine in the Republic of Macedonia (1908-2008).

    PubMed

    Polenakovic, Momir

    2008-12-01

    Arsov Dimitar (Kriva Palanka, 28. IX 1908 - Skopje, 2. VII 1974) - specialist of internal medicine, rheumatologist, Professor at the Medical Faculty of the University of Ss. Cyril and Methodius in Skopje, member of the Macedonian Academy of Sciences and Arts. D. Arsov is the founder of the modern internal medicine in the Republic of Macedonia. He has completed medical studies and specialized in internal medicine at Sorbonne, Paris, France. For 22 years he was the Director of the Clinic for Internal Medicine in Skopje and a Head of the Chair for Internal Medicine of the Medical Faculty in Skopje. He has published over 200 scientific and expert papers and five textbooks, in which he introduced series of medical terms, which entered the Macedonian medical terminology. With his researches he has penetrated in all areas of the internal medicine. An original contribution is his study on intravenous application of adrenalin in the treatment of rheumatic fever and rheumatic endocarditis. He was a member and a head of many medical associations. He received a number of awards. He was promoted for Doctor Honoris Causa at the University of Besanson (France) in 1961. As a great clinician, educator and Professor of internal medicine, and scientist he was one of the most distinguished medical persons of the second part of the XX century in the Republic of Macedonia.

  7. Founder mutation in dystonin-e underlying autosomal recessive epidermolysis bullosa simplex in Kuwait.

    PubMed

    Takeichi, T; Nanda, A; Liu, L; Aristodemou, S; McMillan, J R; Sugiura, K; Akiyama, M; Al-Ajmi, H; Simpson, M A; McGrath, J A

    2015-02-01

    Only two homozygous nonsense mutations in the epidermal isoform of the dystonin gene, DST-e, have been reported previously in autosomal recessive epidermolysis bullosa simplex (EBS); the affected pedigrees were Kuwaiti and Iranian. This subtype of EBS is therefore considered to be a rare clinicopathological entity. In this study, we identified four seemingly unrelated Kuwaiti families in which a total of seven individuals had predominantly acral trauma-induced blistering since infancy. All affected individuals were homozygous for the mutation p.Gln1124* in DST-e, the same mutation that was identified in the originally reported family from Kuwait. Haplotype analysis in the five pedigrees (including the previous case) revealed a shared block of ~60 kb of genomic DNA across the site of the mutation, consistent with a founder effect. Most heterozygotes had no clinical abnormalities although one subject had mild transient skin fragility during childhood, an observation noted in the previously reported Iranian pedigree, suggesting that the condition may also be semidominant in some pedigrees rather than purely autosomal recessive. Our study reveals propagation of a mutant ancestral allele in DST-e throughout Kuwait, indicating that this subtype of EBS may be more common in Kuwait, and perhaps other Middle Eastern countries, than is currently appreciated.

  8. BRCA1 4153delA founder mutation in Russian ovarian cancer patients.

    PubMed

    Krylova, Nadezhda Yu; Lobeiko, Oksana S; Sokolenko, Anna P; Iyevleva, Aglaya G; Rozanov, Maxim E; Mitiushkina, Natalia V; Gergova, Madina M; Porhanova, Tatiana V; Urmancheyeva, Adel F; Maximov, Sergey Ya; Togo, Alexandr V; Imyanitov, Evgeny N

    2006-09-15

    The BRCA1 4153delA allele is frequently referred to as the Russian founder mutation, as it was initially detected in several cancer families from Moscow. Our earlier studies have demonstrated 1% occurrence of BRCA1 4153delA heterozygosity in familial and/or early-onset and/or bilateral Russian breast cancer (BC) patients. Since literature data suggest that the 4153delA variant is more associated with ovarian cancer (OC) than with BC, we expected to reveal a highly elevated frequency of this genotype in Russian ovarian cancer series. However, real-time allele-specific PCR genotyping has detected only two BRCA1 4153delA carriers out of 177 unselected OC patients (1.1%). Both these carriers were early-onset and had serous carcinomas of grade 3. Thus, our study supports neither the Russian origin of BRCA1 4153delA mutation, nor its selectivity towards ovarian versus breast cancer predisposition.

  9. [Detection of a founder mutation in an Argentine family with hereditary non polyposis colorectal cancer].

    PubMed

    Gómez, Laura; Adi, José; Ibarra, Jorge; Roqué, María

    2010-01-01

    Hereditary non polyposis colorectal cancer (HNPCC) has been related to mutations in the DNA mismatch repair genes (MLH1, MSH2 y MSH6). Mutation detection analysis requires the complete sequencing of these genes, given the high frequency of family-specific alterations. A point mutation (2269-2270insT) in the last codon of the MLH1 gene has been detected in families from a northern region of Italy (Reggio Emilia).Given that this alteration was registered only in people from this region, it has been considered a founder mutation. In this work, we present an Argentine HNPCC family whose ancestors were natives from the Reggio Emilia, Italy, and who were carriers for this mutation. In order to detect the genetic alteration, a PCR was developed followed by a restriction enzyme incubation assay. The mutation was detected in 3 family members, two of them without clinical symptoms. The PCR/restriction enzyme methodology has been sensitive and specific for the detection of this mutation. It has allowed the performance of a pre-symptomatic genetic diagnosis in the Argentine HNPCC family, avoiding sending samples abroad. It is worth mentioning that pre-symptomatic diagnosis of hereditary cancers allows enhanced surveillance and support for the affected families when it is performed by a multidisciplinary group.

  10. [Prof. Alfonsas Kaikaris -- the founder of the Lithuanian Pharmacy Museum: his personality and scientific activities].

    PubMed

    Gudiene, Vilma

    2002-01-01

    Alfonsas Kaikaris (1922-1997) was a professor of pharmacy at the Kaunas Medical Institute (now University), historian, museologist, founder of the Lithuanian Pharmacy Museum and of the field of pharmacy history in Lithuania. A. Kaikaris was born in Zagare in 1922. He received his pharmacy diploma in 1947 and began work at the university. Following the reorganization of the university into two institutes, he went to work in the Medical Institute, where he served as the vice dean of the Pharmacy and Stomatology Department from 1957 until 1963. He began to collect pharmaceutical artifacts in 1957. In 1973, the Institute provided a small room in the attic for these objects and so a small pharmacy museum, the first in Lithuania, was born. Thanks to the hard work of A. Kaikaris and others, today this museum has grown into the Pharmacy and Medical History Center of Lithuania, whose work is widely known throughout Europe. A. Kaikaris was also a member of the board of the Lithuanian Scientific Society and head of the Society's Pharmaceutical History Section from 1964 until he retired in 1987. He is the author of 67 scholarly papers and numerous popular articles and conference presentations. In 1988, he received the Paul Stradins Award from the Paul Stradins Medical History Museum in Riga, Latvia, and until his death in 1997 worked as a consultant to the Lithuanian Museum of the History of Medicine and Pharmacy.

  11. Familial Mediterranean Fever (FMF) in Moroccan Jews: Demonstration of a founder effect by extened haplotype analysis

    SciTech Connect

    Aksentijevich, I.; Pras, E.; Helling, S.; Prosen, L.; Kastner, D.L.; Gruberg, L.; Pras, M. )

    1993-09-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The FMF gene (designated MEF') is on 16p, with the gene order 16 cen-D16S80-MEF-D16S94-D16S283-D16S291-16pter. Here the authors report the association of FMF susceptibility with alleles at D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families 14 Moroccan families. For the non-Moroccans, only the allelic association at D16S94 approached statistical significance. Haplotype analysis showed that 18/25 Moroccan FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94-D16S283-D16S291. Among non-Moroccans this haplotype was present in 6/26 FMF chromosomes versus 1/28 controls. Both groups of families are largely descended from Jews who fled the Spanish Inquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic isolation of the Moroccan Jewish community. The lowest haplotype frequency among non-Moroccan carriers may reflect differences both in history and in population genetics. 28 refs., 1 fig., 3 tabs.

  12. Density of founder cells affects spatial pattern formation and cooperation in Bacillus subtilis biofilms.

    PubMed

    van Gestel, Jordi; Weissing, Franz J; Kuipers, Oscar P; Kovács, Akos T

    2014-10-01

    In nature, most bacteria live in surface-attached sedentary communities known as biofilms. Biofilms are often studied with respect to bacterial interactions. Many cells inhabiting biofilms are assumed to express 'cooperative traits', like the secretion of extracellular polysaccharides (EPS). These traits can enhance biofilm-related properties, such as stress resilience or colony expansion, while being costly to the cells that express them. In well-mixed populations cooperation is difficult to achieve, because non-cooperative individuals can reap the benefits of cooperation without having to pay the costs. The physical process of biofilm growth can, however, result in the spatial segregation of cooperative from non-cooperative individuals. This segregation can prevent non-cooperative cells from exploiting cooperative neighbors. Here we examine the interaction between spatial pattern formation and cooperation in Bacillus subtilis biofilms. We show, experimentally and by mathematical modeling, that the density of cells at the onset of biofilm growth affects pattern formation during biofilm growth. At low initial cell densities, co-cultured strains strongly segregate in space, whereas spatial segregation does not occur at high initial cell densities. As a consequence, EPS-producing cells have a competitive advantage over non-cooperative mutants when biofilms are initiated at a low density of founder cells, whereas EPS-deficient cells have an advantage at high cell densities. These results underline the importance of spatial pattern formation for competition among bacterial strains and the evolution of microbial cooperation.

  13. 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.

  14. Founder mutation R245H of Sanfilippo syndrome type A in the Cayman Islands.

    PubMed

    Rady, Peter L; Surendran, Sankar; Vu, Ahn T; Hawkins, Judy C; Michals-Matalon, Kimberlee; Tyring, Stephan K; Merren, Joy; Kumar, Alla K; Matalon, Reuben

    2002-01-01

    Sanfilippo A syndrome is an autosomal recessive lysosomal storage disease. This disease was reported in the Cayman Islands population with carrier frequency of 1/7 to 1/10 in the West Bay district of Grand Cayman. The carrier testing of Sanfilippo A disease for families at risk was carried out using the thermal characteristics of sulfamidase activity. In the present study, a search for mutations in the sulfamidase gene in an index family was performed. In addition, 77 individuals, relatives of children with Sanfilippo A syndrome, were also studied by single-strand conformation polymorphism (SSCP), restriction fragment-length polymorphism (RFLP) analyses, and sequencing. A single mutation, G746A (R245H), was found in the family, with the patient being homozygous and both parents and 1 of the 3 siblings being carriers. Among the 77 family members of the patient with Sanfilippo syndrome, the same mutation was found among carriers of the disease. The finding of a single mutation supports the idea of a founder effect, which facilitates accurate carrier identification of Sanfilippo A syndrome in the population of Cayman Islands.

  15. Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

    PubMed Central

    Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

    2017-01-01

    Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks. PMID:28276459

  16. Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

    NASA Astrophysics Data System (ADS)

    Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

    2017-03-01

    Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks.

  17. Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in Northeastern Brazil.

    PubMed

    Manzoli, Gabrielle N; Bademci, Guney; Acosta, Angelina X; Félix, Têmis M; Cengiz, F Basak; Foster, Joseph; Da Silva, Danniel S Dias; Menendez, Ibis; Sanchez-Pena, Isalis; Tekin, Demet; Blanton, Susan H; Abe-Sandes, Kiyoko; Liu, Xue Zhong; Tekin, Mustafa

    2016-11-01

    Identifying the genetic etiology in a person with hearing loss (HL) is challenging due to the extreme genetic heterogeneity in HL and the population-specific variability. In this study, after excluding GJB2 variants, targeted resequencing of 180 deafness-related genes revealed the causative variants in 11 of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic variants were in MYO15A (10 families) and CLDN14 (one family). Remarkably, the MYO15A p.(Val1400Met) variant was identified in eight families from the city of Monte Santo in the northeast region of Brazil. Haplotype analysis of this variant was consistent with a single founder. No other cases with this variant were detected among 105 simplex cases from other cities of northeastern Brazil, suggesting that this variant is confined to a geographical region. This study suggests that it is feasible to develop population-specific screening for deafness variants once causative variants are identified in different geographical groups.

  18. Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a cuban founder-effect population

    PubMed Central

    Auburger, Georg; Diaz, Guillermo Orozco; Capote, Raul Ferreira; Sanchez, Suzana Gispert; Perez, Marta Paradoa; del Cueto, Marianela Estrada; Meneses, Mirna Garcia; Farrall, Martin; Williamson, Robert; Chamberlain, Susan; Baute, Luis Heredero

    1990-01-01

    The locus for autosomal dominant ataxia with a diagnosis of olivo-ponto-cerebellar atrophy at autopsy has been previously assigned to chromosome 6p. However, evidence for two alternative locations has been reported. We have recently described a large potential founder-effect population of such patients in the Holguin province of Cuba. With an estimated 1,000 patients available for analysis, this extensive cluster of families provides a unique opportunity for the definitive localization of the genetic mutation. Linkage analysis between the disease locus in this population and markers within and flanking the HLA region on chromosome 6 were undertaken in 12 families comprising over 100 affected individuals. Despite similarity in the clinical phenotype between those families where the disease locus has been reported to be linked to the HLA locus and the Cuban patients, no evidence of linkage to this region could be demonstrated in the latter. The disease locus was excluded from a 96-cM genetic interval of the short arm of chromosome 6, encompassing the F13A1–HLA–GLO1–MUT/D6S4 loci. These data strongly support the existence of genetic heterogeneity for the disease. PMID:1971152

  19. Genomic complexity of the Y-STR DYS19: inversions, deletions and founder lineages carrying duplications.

    PubMed

    Balaresque, Patricia; Parkin, Emma J; Roewer, Lutz; Carvalho-Silva, Denise R; Mitchell, R John; van Oorschot, Roland A H; Henke, Jürgen; Stoneking, Mark; Nasidze, Ivan; Wetton, Jon; de Knijff, Peter; Tyler-Smith, Chris; Jobling, Mark A

    2009-01-01

    The Y-STR DYS19 is firmly established in the repertoire of Y-chromosomal markers used in forensic analysis yet is poorly understood at the molecular level, lying in a complex genomic environment and exhibiting null alleles, as well as duplications and occasional triplications in population samples. Here, we analyse three null alleles and 51 duplications and show that DYS19 can also be involved in inversion events, so that even its location within the short arm of the Y chromosome is uncertain. Deletion mapping in the three chromosomes carrying null alleles shows that their deletions are less than approximately 300 kb in size. Haplotypic analysis with binary markers shows that they belong to three different haplogroups and so represent independent events. In contrast, a collection of 51 DYS19 duplication chromosomes belong to only four haplogroups: two are singletons and may represent somatic mutation in lymphoblastoid cell lines, but two, in haplogroups G and C3c, represent founder lineages that have spread widely in Central Europe/West Asia and East Asia, respectively. Consideration of candidate mechanisms underlying both deletions and duplications provides no evidence for the involvement of non-allelic homologous recombination, and they are likely to represent sporadic events with low mutation rates. Understanding the basis and population distribution of these DYS19 alleles will aid in the utilisation and interpretation of profiles that contain them.

  20. [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).

  1. 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.

  2. 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.

  3. 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.

  4. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection

    PubMed Central

    Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Keele, Brandon F.; Learn, Gerald H.; Giorgi, Elena E.; Li, Hui; Decker, Julie M.; Wang, Shuyi; Baalwa, Joshua; Kraus, Matthias H.; Parrish, Nicholas F.; Shaw, Katharina S.; Guffey, M. Brad; Bar, Katharine J.; Davis, Katie L.; Ochsenbauer-Jambor, Christina; Kappes, John C.; Saag, Michael S.; Cohen, Myron S.; Mulenga, Joseph; Derdeyn, Cynthia A.; Allen, Susan; Hunter, Eric; Markowitz, Martin; Hraber, Peter; Perelson, Alan S.; Bhattacharya, Tanmoy; Haynes, Barton F.; Korber, Bette T.; Hahn, Beatrice H.

    2009-01-01

    Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4+ T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12–20 mo, viruses exhibited concentrated mutations at 17–34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses. PMID:19487424

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

    PubMed Central

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

    1996-01-01

    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. Images Figure 2 Figure 4 PMID:8751865

  6. 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.

  7. Effect of maternal aging on transgene heritability in transgenic founder mice derived from zygotes microinjected with retroviral long terminal repeat-containing recombinant deoxyribonucleic acid.

    PubMed

    Wang, T H; Yang, W K; Hoyt, P R; Ch'ang, L Y; Savin, T J

    1993-05-01

    To determine the stability of artificially introduced recombinant DNA in the mouse germline throughout the reproductive life, founder mice derived from fertilized eggs injected with retroviral long-terminal-repeat-containing recombinant DNAs were mated with congenic FVB/N mice. Tail DNA of all progeny were screened and restriction fragment patterns of the transgenes were examined. Litter size and percentage of transgene transmission at various reproductive age periods were analyzed. Microinjection of 1737 eggs with four different recombinant DNAs resulted in 12 female and 11 male transgenic mice; 2 males were sterile and the remaining 21 mice served as founders to produce 1087 F1 progeny. With increasing parental age, litter size decreased generally. The percentage of progeny inheriting the transgenes declined markedly with increasing aging of 4 female founders; this aging effect was not observed in male founders (p < 0.005). No apparent change in transgenes was detected in progeny from late reproductive stages.

  8. 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

  9. Counting the founders: the matrilineal genetic ancestry of the Jewish Diaspora.

    PubMed

    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

    2008-04-30

    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.

  10. 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

  11. 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.

  12. 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.

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

    PubMed Central

    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.

    2015-01-01

    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

  14. Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia.

    PubMed

    Marrosu, M G; Murru, R; Murru, M R; Costa, G; Zavattari, P; Whalen, M; Cocco, E; Mancosu, C; Schirru, L; Solla, E; Fadda, E; Melis, C; Porru, I; Rolesu, M; Cucca, F

    2001-12-01

    Several studies have indicated that multiple sclerosis (MS) is associated and linked to the major histocompatibility complex (MHC)/human leukocyte antigen (HLA) region of chromosome 6p21.3, but the exact location and nature of the primarily associated locus within the HLA complex is still controversial and largely presumptive. By linkage disequilibrium mapping, we have systematically investigated this chromosome region in the founder population of Sardinia to determine the relative associations of the various loci with MS. An overall 11.4 Mb region, which encompasses the whole HLA complex, was scanned with 19 microsatellite markers and with single nucleotide polymorphisms within 12 functional candidate genes and assessed for MS association using the extended transmission disequilibrium test (ETDT). A peak of association represented by the three adjacent DRB1, -DQA1 and -DQB1 loci was detected in the class II region. Two additional less significant areas of association were detected, respectively, in the centromeric side of the class II region at the DPB1 locus and, telomeric of the classically defined class I loci, at the D6S1683 microsatellite. Conditional ETDT analysis indicated that these regions of association could be independent of each other. Within the main peak of association, DRB1 and DQB1 contribute to the disease association independently of each other whereas DQA1 had no detectable primary genetic effects. We evaluated the haplotype distribution at the region showing the strongest association and found five DQB1-DRB1 haplotypes positively associated with MS in Sardinia. These consistently included all the haplotypes previously found associated with MS in the various human populations, thus supporting a primary effect of the products of these loci in MS. Overall these results are consistent with a multilocus model of the MHC encoded susceptibility to MS.

  15. A founder mutation in the CLCNKB gene causes Bartter syndrome type III in Spain.

    PubMed

    Rodríguez-Soriano, Juan; Vallo, Alfredo; Pérez de Nanclares, Gustavo; Bilbao, José Ramón; Castaño, Luis

    2005-07-01

    The term "Bartter syndrome" encompasses a group of closely related inherited tubulopathies characterized by markedly reduced NaCl transport by the distal nephron. At present, five different genetic variants have been demonstrated. The majority of patients with so-called classic Bartter syndrome carry inactivating mutations of the CLCNKB gene encoding the basolateral ClC-Kb chloride channel (Bartter syndrome type III). The purpose of this study was to investigate the underlying mutation in cases of classic Bartter syndrome followed at our center. Ten patients, including two sisters, with clinical and biochemical features of classic Bartter syndrome were included in the mutational analysis. They originated from different regions of Spain with either Basque or Spanish ancestry. There was no history of consanguineous marriage in any of the kindreds. The parents and siblings of each patient, as well as a population of 300 healthy control adult subjects, were also analyzed. All ten patients were found to be homozygous for an identical missense mutation in the CLCNKB gene, substituting a threonine for an alanine at codon 204 (A204T) in the putative fifth transmembrane domain of the protein. None of the 300 control subjects were homozygous for the A204T allele. Overall, the A204T mutation was detected on 2/600 control chromosomes. Despite sharing a common mutation, the clinical manifestations of the syndrome in the patients varied from lack of symptoms to severe growth retardation. Demonstration of a point mutation within the CLCNKB gene as the apparently unique cause of Bartter syndrome type III in Spain is highly suggestive of a founder effect. Our results also support the lack of correlation between genotype and phenotype in this disease.

  16. 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.

  17. [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

  18. 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.

  19. Origin and number of founders in an introduced insular primate: estimation from nuclear genetic data.

    PubMed

    Bonhomme, M; Blancher, A; Cuartero, S; Chikhi, L; Crouau-Roy, B

    2008-02-01

    Cynomolgus macaques (Macaca fascicularis) were introduced on the island of Mauritius between 400 and 500 years ago and underwent a strong population expansion after a probable initial founding event. However, in practice, little is known of the geographical origin of the individuals that colonized the island, on how many individuals were introduced, and of whether the following demographic expansion erased any signal of this putative bottleneck. In this study, we asked whether the current nuclear genome of the Mauritius population retained a signature that would allow us to answer these questions. Altogether, 21 polymorphic autosomal and sex-linked microsatellites were surveyed from 81 unrelated Mauritius individuals and 173 individuals from putative geographical sources in Southeast Asia: Java, the Philippines islands and the Indochinese peninsula. We found that (i) the Mauritius population was closer to different populations depending on the markers we used, which suggests a possible mixed origin with Java playing most probably a major role; and (ii) the level of diversity was lower than the other populations but there was no clear and consistent bottleneck signal using either summary statistics or full-likelihood methods. However, summary statistics strongly suggest that Mauritius is not at mutation-drift equilibrium and favours an expansion rather than a bottleneck. This suggests that on a short time scale, population decline followed by growth can be difficult to deduce from genetic data based on mutation-drift theory. We then used a simple Bayesian rejection algorithm to estimate the number of founders under different demographic models (exponential, logistic and logistic with lag) and pure genetic drift. This new method uses current population size estimates and expected heterozygosity of Mauritius and source population(s). Our results indicate that a simple exponential growth is unlikely and that, under the logistic models, the population may have expanded

  20. OPTN 691_692insAG is a founder mutation causing recessive ALS and increased risk in heterozygotes

    PubMed Central

    Goldstein, Orly; Nayshool, Omri; Nefussy, Beatrice; Traynor, Bryan J.; Renton, Alan E.; Gana-Weisz, Mali; Drory, Vivian E.

    2016-01-01

    Objective: To detect genetic variants underlying familial and sporadic amyotrophic lateral sclerosis (ALS). Methods: We analyzed 2 founder Jewish populations of Moroccan and Ashkenazi origins and ethnic matched controls. Exome sequencing of 2 sisters with ALS from Morocco was followed by genotyping the identified causative null mutation in 379 unrelated patients with ALS and 1,000 controls. The shared risk haplotype was characterized using whole-genome single nucleotide polymorphism array. Results: We identified 5 unrelated patients with ALS homozygous for the null 691_692insAG mutation in the optineurin gene (OPTN), accounting for 5.8% of ALS of Moroccan origin and 0.3% of Ashkenazi. We also identified a high frequency of heterozygous carriers among patients with ALS, 8.7% and 2.9%, respectively, compared to 0.75% and 1.0% in controls. The risk of carriers for ALS was significantly increased, with odds ratio of 13.46 and 2.97 in Moroccan and Ashkenazi Jews, respectively. We determined that 691_692insAG is a founder mutation in the tested populations with a minimal risk haplotype of 58.5 Kb, encompassing the entire OPTN gene. Conclusions: Our data show that OPTN 691_692insAG mutation is a founder mutation in Moroccan and Ashkenazi Jews. This mutation causes autosomal recessive ALS and significantly increases the risk to develop the disease in heterozygous carriers, suggesting both a recessive mode of inheritance and a dominant with incomplete penetrance. These data emphasize the important role of OPTN in ALS pathogenesis, and demonstrate the complex genetics of ALS, as the same mutation leads to different phenotypes and appears in 2 patterns of inheritance. PMID:26740678

  1. 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.

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

    PubMed Central

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

    2016-01-01

    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

  3. Mutations in COL27A1 cause Steel syndrome and suggest a founder mutation effect in the Puerto Rican population

    PubMed Central

    Gonzaga-Jauregui, Claudia; Gamble, Candace N; Yuan, Bo; Penney, Samantha; Jhangiani, Shalini; Muzny, Donna M; Gibbs, Richard A; Lupski, James R; Hecht, Jacqueline T

    2015-01-01

    Osteochondrodysplasias represent a large group of developmental structural disorders that can be caused by mutations in a variety of genes responsible for chondrocyte development, differentiation, mineralization and early ossification. The application of whole-exome sequencing to disorders apparently segregating as Mendelian traits has proven to be an effective approach to disease gene identification for conditions with unknown molecular etiology. We identified a homozygous missense variant p.(Gly697Arg) in COL27A1, in a family with Steel syndrome and no consanguinity. Interestingly, the identified variant seems to have arisen as a founder mutation in the Puerto Rican population. PMID:24986830

  4. William Cooke MD MRCS (1785-1873) - General Practitioner, Founder of the Hunterian Society and Deacon of the Congregational Church.

    PubMed

    Selley, Peter

    2015-12-21

    Farmer's son William Cooke completed his medical training at Barts before embarking on a 60-year career as a general practitioner in and around London. In 1819, he was a co-founder, and for 20 years secretary, of the Hunterian Society which continues to provide education to its members. He was the author of several books where his views on the importance of post-mortem examinations and the interrelationships of body and mind in disease were discussed. He was a prominent non-conformist and became a deacon in the Congregational Church. He died in 1873, aged 87.

  5. [Shestov V I--the founder of the Department of Organisation and tactics of the naval medical services].

    PubMed

    Chernikov, O G; Chernyĭ, V S; Mishin, Iu A; Soshkin, P A

    2014-11-01

    Vasilii Ivanovich Shestov during the Great Patriotic War performed various tasks concerning the organization of medical support in the Leningrad naval base, consulted on an issue of production and use of hospital and medical transport ships, worked on the organization of medical support in Schliessburg and etc. Shestov performed a considerable amount of research and methodological works concerning the establishment of the discipline "Organisation of naval medical support". He is considered as one of the founders of the theory of naval medical evacuation support.

  6. 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

  7. The MSH2 c.388_389del mutation shows a founder effect in Portuguese Lynch syndrome families.

    PubMed

    Pinheiro, M; Pinto, C; Peixoto, A; Veiga, I; Mesquita, B; Henrique, R; Lopes, P; Sousa, O; Fragoso, M; Dias, L M; Baptista, M; Marinho, C; Mangold, E; Vaccaro, C; Evans, D G; Farrington, S; Dunlop, M G; Teixeira, M R

    2013-09-01

    The MSH2 c.388_389del mutation has occasionally been described in Lynch families worldwide. At the Portuguese Oncology Institute in Porto, Portugal, we have identified 16 seemingly unrelated families with this germline mutation. To evaluate if this alteration is a founder or a recurrent mutation we performed haplotype analysis in the 16 Portuguese index cases and 55 relatives, as well as in four index cases and 13 relatives reported from Germany, Scotland, England, and Argentina. In the Portuguese families we observed a shared haplotype of approximately 10 Mb and all were originated from the north of Portugal. These results suggest that this alteration is a founder mutation in Portugal with a relatively recent origin. In the reported families outside Portugal with this mutation different haplotype backgrounds were observed, supporting the hypothesis that it occurred de novo on multiple occasions. We also conclude that the high proportion of families with the MSH2 c.388_389del mutation indicates that screening for this alteration as a first step may be cost-effective in the genetic testing of Lynch syndrome suspects of Portuguese ancestry, especially those originating from the north of Portugal.

  8. A founder large deletion mutation in Xeroderma pigmentosum-Variant form in Tunisia: implication for molecular diagnosis and therapy.

    PubMed

    Ben Rekaya, Mariem; Laroussi, Nadia; Messaoud, Olfa; Jones, Mariem; Jerbi, Manel; Naouali, Chokri; 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.

  9. A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman.

    PubMed

    Palombo, Flavia; Al-Wardy, Nadia; Ruscone, Guido Alberto Gnecchi; Oppo, Manuela; Kindi, Mohammed Nasser Al; Angius, Andrea; Al Lamki, Khalsa; Girotto, Giorgia; Giangregorio, Tania; Benelli, Matteo; Magi, Alberto; Seri, Marco; Gasparini, Paolo; Cucca, Francesco; Sazzini, Marco; Al Khabori, Mazin; Pippucci, Tommaso; Romeo, Giovanni

    2017-02-01

    The increased risk for autosomal recessive disorders is one of the most well-known medical implications of consanguinity. In the Sultanate of Oman, a country characterized by one of the highest rates of consanguineous marriages worldwide, prevalence of genetic hearing loss (GHL) is estimated to be 6/10 000. Families of GHL patients have higher consanguinity rates than the general Omani population, indicating a major role for recessive forms. Mutations in GJB2, the most commonly mutated GHL gene, have been sporadically described. We collected 97 DNA samples of GHL probands, affected/unaffected siblings and parents from 26 Omani consanguineous families. Analyzing a first family by whole-exome sequencing, we identified a novel homozygous frameshift duplication (c.1171_1177dupGCCATCT) in MYO15A, the gene linked to the deafness locus DFNB3. This duplication was then found in a total of 8/26 (28%) families, within a 849 kb founder haplotype. Reconstruction of haplotype structure at MYO15A surrounding genomic regions indicated that the founder haplotype branched out in the past two to three centuries from a haplotype present worldwide. The MYO15A duplication emerges as the major cause of GHL in Oman. These findings have major implications for the design of GHL diagnosis and prevention policies in Oman.

  10. Fabry disease: Evidence for a regional founder effect of the GLA gene mutation 30delG in Brazilian patients.

    PubMed

    de Alencar, Dayse Oliveira; Netto, Cristina; Ashton-Prolla, Patricia; Giugliani, Roberto; Ribeiro-Dos-Santos, Ândrea; Pereira, Fernanda; Matte, Ursula; Santos, Ney; Santos, Sidney

    2014-01-01

    The Fabry disease is caused by mutations in the gene (GLA) that encodes the enzyme α-galactosidase A (α-Gal A). More than 500 pathologic variants of GLA have already been described, most of them are family-specific. In southern Brazil, a frequent single-base deletion (GLA 30delG) was identified among four families that do not recognize any common ancestral. In order to investigate the history of this mutation (investigate the founder effect, estimate the mutation age and the most likely source), six gene-flanking microsatellite markers of the X chromosome on the mutation carriers and their parents, 150 individuals from the same population and 300 individuals that compose the Brazilian parental populations (Europeans, Africans and Native Americans) were genotyped. A common haplotype to the four families was identified and characterized as founder. The age was estimated with two statistics software (DMLE 2.2 and ESTIAGE) that agreed with 11 to 12 generations old. This result indicates that the mutation GLA 30delG was originated from a single event on the X chromosome of a European immigrant, during the southern Brazil colonization between 1710 and 1740.

  11. Estimation of the Effective Number of Founders That Initiate an Infection after Aphid Transmission of a Multipartite Plant Virus ▿

    PubMed Central

    Betancourt, Mónica; Fereres, Alberto; Fraile, Aurora; García-Arenal, Fernando

    2008-01-01

    The fecundity of RNA viruses can be very high. Thus, it is often assumed that viruses have large populations, and RNA virus evolution has been mostly explained using purely deterministic models. However, population bottlenecks during the virus life cycle could result in effective population numbers being much smaller than reported censuses, and random genetic drift could be important in virus evolution. A step at which population bottlenecks may be severe is host-to-host transmission. We report here an estimate of the size of the population that starts a new infection when Cucumber mosaic virus (CMV) is transmitted by the aphid Aphis gossypii, based on the segregation of two CMV genotypes in plants infected by aphids that acquired the virus from plants infected by both genotypes. Results show very small effective numbers of founders, between one and two, both in experiments in which the three-partite genome of CMV was aphid transmitted and in experiments in which a fourth RNA, CMV satellite RNA, was also transmitted. These numbers are very similar to those published for Potato virus Y, which has a monopartite genome and is transmitted by aphids according to a different mechanism than CMV. Thus, the number of genomic segments seems not to be a major determinant of the effective number of founders. Also, our results suggest that the occurrence of severe bottlenecks during horizontal transmission is general for viruses nonpersistently transmitted by aphids, indicating that random genetic drift should be considered when modeling virus evolution. PMID:18842732

  12. 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.

  13. Nucleotide Variation, Linkage Disequilibrium and Founder-Facilitated Speciation in Wild Populations of the Zebra Finch (Taeniopygia guttata)

    PubMed Central

    Balakrishnan, Christopher N.; Edwards, Scott V.

    2009-01-01

    The zebra finch has long been an important model system for the study of vocal learning, vocal production, and behavior. With the imminent sequencing of its genome, the zebra finch is now poised to become a model system for population genetics. Using a panel of 30 noncoding loci, we characterized patterns of polymorphism and divergence among wild zebra finch populations. Continental Australian populations displayed little population structure, exceptionally high levels of nucleotide diversity (π = 0.010), a rapid decay of linkage disequilibrium (LD), and a high population recombination rate (ρ ≈ 0.05), all of which suggest an open and fluid genomic background that could facilitate adaptive variation. By contrast, substantial divergence between the Australian and Lesser Sunda Island populations (KST = 0.193), reduced genetic diversity (π = 0.002), and higher levels of LD in the island population suggest a strong but relatively recent founder event, which may have contributed to speciation between these populations as envisioned under founder-effect speciation models. Consistent with this hypothesis, we find that under a simple quantitative genetic model both drift and selection could have contributed to the observed divergence in six quantitative traits. In both Australian and Lesser Sundas populations, diversity in Z-linked loci was significantly lower than in autosomal loci. Our analysis provides a quantitative framework for studying the role of selection and drift in shaping patterns of molecular evolution in the zebra finch genome. PMID:19047416

  14. Haplotype study of West European and North African Unverricht-Lundborg chromosomes: evidence for a few founder mutations.

    PubMed

    Moulard, Bruno; Genton, Pierre; Grid, Djamel; Jeanpierre, Marc; Ouazzani, Réda; Mrabet, Amel; Morris, Mike; LeGuern, Eric; Dravet, Charlotte; Mauguière, François; Utermann, Barbara; Baldy-Moulinier, Michel; Belaidi, Halima; Bertran, Françoise; Biraben, Arnaud; Ali Chérif, André; Chkili, Taieb; Crespel, Arielle; Darcel, Françoise; Dulac, Olivier; Geny, Christian; Humbert-Claude, Véronique; Kassiotis, Philippe; Buresi, Catherine; Malafosse, Alain

    2002-09-01

    Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy common in Finland and North Africa, and less common in Western Europe. ULD is mostly caused by expansion of a dodecamer repeat in the cystatin B gene ( CSTB) promoter. We performed a haplotype study of ULD chromosomes (ULDc) with the repeat expansion. We included 48 West European Caucasian (WEC) and 47 North African (NA) ULDc. We analysed eight markers flanking CSTB(GT10-D21S1890-D21S1885-D21S2040-D21S1259- CSTB-D21S1912-PFKL-D21S171) and one intragenic variant in the CSTB 3' UTR (A2575G). We observed a founder effect in most of the NA ULD patients, as 61.7% of the NA ULDc (29/47) shared the same haplotype, A1 (1-1-A-1-6-7), for markers D21S1885-D21S2040-A2575G-D21S1259-D21S1912-PFKL. Moreover, if we considered only the markers D21S1885, D21S2040, A2575G and D21S1259, 43 of the 47 NA ULDc shared the same alleles 1-1-A-1, haplotype A. As previously shown, the WEC ULDc were heterogeneous. However, the Baltic haplotype, A3 (5-1-1-A-1-1), was observed in ten WEC ULDc (20.8%) and the CSTB 3'UTR variant, which we called the Alps variant, was observed in 17 ULDc (35.4%). Finally, as almost all NA patients, like Scandinavian patients, were of the haplotype A, we assumed that there was an ancient common founder effect in NA and Baltic ULD patients. We estimated that the putative most recent common ancestral ULD carrier with this haplotype A must have existed about 2,500 years ago (100-150 generations). Finally, this work provides evidence for the existence of only a small number of founder mutations in ULD.

  15. 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".

  16. [Max Isserlin, Kantian orientation at Königsberg, psychotherapist with Kraepelin, founder of child psychiatry at Munich, emigrant to Britain].

    PubMed

    Peters, U H

    2002-01-01

    This account of the life and work of Max Isserlin (1879 - 1941) wants to be a reminder of a German-Jewish fate next to Kraepelin and as a forced emigrant. Immediately after his studies at Königsberg Isserlin in 1903 came to Kraepelin at Heidelberg, later he followed him to Munich. All his life he kept a Kantian orientation and defended Kraepelin's positions out of this background. Kraepelin entrusted to him all of psychotherapy, theory and practice, which Isserlin for at least 18 years gave courses of in Kraepelin's department. His textbook of psychotherapy thus transmissions Kraepelins convictions about this topic also. During World War I Isserlin was the head of a field-hospital for brain damaged soldiers and continued working this way after the end of the war. Finally he became the founder of child psychiatry in Munich, until he was forced to leave Germany for Britain with a heavy heart.

  17. A founder mutation in ADAMTSL4 causes early-onset bilateral ectopia lentis among Jews of Bukharian origin.

    PubMed

    Reinstein, Eyal; Smirin-Yosef, Pola; Lagovsky, Irina; Davidov, Bella; Peretz Amit, Gabriela; Neumann, Doron; Orr-Urtreger, Avi; Ben-Shachar, Shay; Basel-Vanagaite, Lina

    2016-01-01

    The term isolated ectopia lentis (EL; subluxation or dislocation of the human crystalline lens) is applied to patients with EL, without skeletal features and in the absence of aortic root dilatation. To date, the only gene shown to cause autosomal-recessive isolated EL is ADAMTSL4. Here we report a novel founder mutation in ADAMTSL4 gene in children of Bukharian Jewish origin presenting with early-onset bilateral EL. A carrier frequency of 1:48 was determined among unrelated healthy Bukharian Jews. Given the complications associated with disease and the allele frequency, a population screening for individuals of this ancestry is warranted in order to allow prenatal, pre-implantation or early postnatal diagnosis.

  18. Impact on electroencephalography of Adolf Beck, a prominent Polish scientist and founder of the Lviv School of Physiology.

    PubMed

    Zayachkivska, Oksana; Gzhegotsky, Mechyslav; Coenen, Anton

    2012-07-01

    Adolf Beck (1863-1942) can be regarded as the co-founder of electroencephalography. His studies on the cerebral cortex of animals have facilitated the introduction of the electroencephalogram (EEG) as a main tool for studying the brain. The localization of senses on the cortex with evoked potentials and the description of the desynchronization of the electrical brain activity upon stimulation, are hallmarks of the research of Beck. He performed his groundbreaking studies under supervision of the famous Napoleon Cybulski at the Jagiellonian University in Cracow (Poland) between 1888 and 1895. In that last year Beck was appointed professor at the University of Lemberg (Lviv), where he founded the Department of Physiology and recruited scientists to the Lviv School of Physiology. Beck was the leading authority of the University of Lemberg in the most turbulent period of the town's history. Together with Cybulski he wrote the influential textbook 'Human physiology' in 1915.

  19. ["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.

  20. A common variant in CLDN14 causes precipitous, prelingual sensorineural hearing loss in multiple families due to founder effect.

    PubMed

    Pater, Justin A; Benteau, Tammy; Griffin, Anne; Penney, Cindy; Stanton, Susan G; Predham, Sarah; Kielley, Bernadine; Squires, Jessica; Zhou, Jiayi; Li, Quan; Abdelfatah, Nelly; O'Rielly, Darren D; Young, Terry-Lynn

    2017-01-01

    Genetic isolates provide unprecedented opportunities to identify pathogenic mutations and explore the full natural history of clinically heterogeneous phenotypes such as hearing loss. We noticed a unique audioprofile, characterized by prelingual and rapid deterioration of hearing thresholds at frequencies >0.5 kHz in several adults from unrelated families from the island population of Newfoundland. Targeted serial Sanger sequencing of probands for deafness alleles (n = 23) that we previously identified in this founder population was negative. Whole exome sequencing in four members of the largest family (R2010) identified a CLDN14 (DFNB29) variant [c.488C>T; p. (Ala163Val)], likely pathogenic, sensorineural hearing loss, autosomal recessive. Although not associated with deafness or disease, CLDN14 p.(Ala163Val) has been previously reported as a variant of uncertain significance (VUS). Targeted sequencing of 169 deafness probands identified one homozygote and one heterozygous carrier. Genealogical studies, cascade sequencing and haplotype analysis across four unrelated families showed all subjects with the unique audioprofile (n = 12) were also homozygous for p.(Ala163Val) and shared a 1.4 Mb DFNB29-associated haplotype on chromosome 21. Most significantly, sequencing 175 population controls revealed 1% of the population are heterozygous for CLDN14 p.(Ala163Val), consistent with a major founder effect in Newfoundland. The youngest CLDN14 [c.488C>T; p.(Ala163Val)] homozygote passed newborn screening and had normal hearing thresholds up to 3 years of age, which then deteriorated to a precipitous loss >1 kHz during the first decade. Our study suggests that genetic testing may be necessary to identify at-risk children in time to prevent speech, language and developmental delay.

  1. 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.

  2. 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

  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. 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.

  5. 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…

  6. Colleges and Universities as Historic Institutions: a Study of the Historical Context of Campus Architecture: Founders Hall, Virginia Commonwealth University, Richmond, Virginia.

    ERIC Educational Resources Information Center

    Shultz, James A.

    A study of Founders Hall at the Virginia Commonwealth University (VCU) explores the history of that building and its symbolic role for the campus and the institution. The building was originally a residence built in the late 19th century and was later the location of the Richmond School of Social Work and Public Policy and of the Richmond…

  7. 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.

  8. Friedreich ataxia in Louisiana Acadians: demonstration of a founder effect by analysis of microsatellite-generated extended haplotypes.

    PubMed Central

    Sirugo, G; Keats, B; Fujita, R; Duclos, F; Purohit, K; Koenig, M; Mandel, J L

    1992-01-01

    Eleven Acadian families with Friedreich ataxia (FA) who were from southwest Louisiana were studied with a series of polymorphic markers spanning 310 kb in the D9S5-D9S15 region previously shown to be tightly linked to the disease locus. In particular, three very informative microsatellites were tested. Evidence for a strong founder effect was found, since a specific extended haplotype spanning 230 kb from 26P (D9S5) to MCT112 (D9S15) was present on 70% of independent FA chromosomes and only once (6%) on the normal ones. There was no evident correlation between haplotypes and clinical expression. The typing of an additional microsatellite (GS4) located 80 kb from MCT112 created a divergence of the main FA-linked haplotype, generating four minor and one major haplotype. A similar split was observed with GS4 in a patient homozygous for a rare 26P-to-MCT112 haplotype. These results suggest that GS4 is flanking marker for the disease locus, although other interpretations are possible. Images Figure 2 PMID:1347194

  9. 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

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

    PubMed

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

    2013-07-07

    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.

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

    PubMed

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

    2011-10-01

    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.

  13. History of settlement of villages from Central Tunisia by studying families sharing a common founder Glycogenosis type III mutation.

    PubMed

    Rhouma, Faten Ben; Messai, Habib; Hsouna, Sana; Halim, Nizar Ben; Cherif, Wafa; Fadhel, Sihem Ben; Tiar, Afaf; Nagara, Majdi; Azzouz, Hatem; Sfar, Mohamed-Tahar; Dridi, Marie-Françoise Ben; Tebib, Neji; Ayadi, Abdelkarim; Abdelhak, Sonia; Kefi, Rym

    2016-09-01

    Glycogen storage disease type III (GSD III; Cori disease; Forbes disease) is an autosomal recessive inherited metabolic disorder resulting from deficient glycogen debrancher enzyme activity in liver and muscle. In this study, we focused on a single AGL gene mutation p.W1327X in 16 Tunisian patients from rural area surrounding the region of Mahdia in Central Tunisia. This constitutes the largest pool of patients with this mutation ever described. This study was performed to trace the history of the patients' ancestries in a single region. After extraction of genomic DNA, exon 31 of AGL gene was sequenced. The patients were investigated for the hypervariable segment 1 of mitochondrial DNA and 17 Y-STR markers. We found that the p.W1327X mutation was a founder mutation in Tunisia Analysis of maternal lineages shows an admixture of autochthonous North African, sub-Saharan and a predominance of Eurasian haplogroups. Heterogeneity of maternal haplogroups indicates an ancient settlement. However, paternal gene flow was highly homogeneous and originates from the Near East. We hypothesize that the p.W1327X mutation was introduced into the Tunisian population probably by a recent migration event; then the mutation was fixed in a small region due to the high rate of consanguineous marriages and genetic drift. The screening for this mutation should be performed in priority for GSD III molecular diagnosis, for patients from the region of Mahdia and those from regions sharing the same settlement history.

  14. 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.

  15. [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.

  16. 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.

  17. Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China.

    PubMed

    Li, Fan; Ma, Liying; Feng, Yi; Hu, Jing; Ni, Na; Ruan, Yuhua; Shao, Yiming

    2017-03-02

    HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines.

  18. A sea urchin homologue of the chordate Brachyury (T) gene is expressed in the secondary mesenchyme founder cells.

    PubMed

    Harada, Y; Yasuo, H; Satoh, N

    1995-09-01

    Chordates are thought to have emerged from some common ancestor of deuterostomes by organizing shared anatomical and embryological features including a notochord, a dorsal nerve cord and pharyngeal gill slits. Because the notochord is the most prominent feature of chordates and because the Brachyury (T) gene is essential for notochord formation, the T gene is a key molecular probe with which to explore the origin and evolution of chordates. We investigated whether the sea urchin (echinoderm) conserves the T gene and, if so, where the sea urchin T gene is expressed. A cDNA clone for the sea urchin T (HpTa) gene contained a long open reading frame that encodes a polypeptide of 434 amino acids. Although the overall degree of amino acid identity was not very high (52%, sea urchin/mouse), in the T domain of the N terminus the amino acid identity was 73% (sea urchin/mouse). The HpTa gene is present as a single copy per haploid genome. As with the chordate T gene, the expression of HpTa is transient, being first detected in the swimming blastula, maximally transcribed in the gastrula, decreasing at the prism larval stage and barely detectable at the pluteus larval stage. HpTa transcripts were found in the secondary mesenchyme founder cells, vegetal plate of the mesenchyme blastula, extending tip of the invaginating archenteron and, finally, the secondary mesenchyme cells at the late-gastrula stage.(ABSTRACT TRUNCATED AT 250 WORDS)

  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. Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes.

    PubMed

    Asmal, Mohammed; Luedemann, Corinne; Lavine, Christy L; Mach, Linh V; Balachandran, Harikrishnan; Brinkley, Christie; Denny, Thomas N; Lewis, Mark G; Anderson, Hanne; Pal, Ranajit; Sok, Devin; Le, Khoa; Pauthner, Matthias; Hahn, Beatrice H; Shaw, George M; Seaman, Michael S; Letvin, Norman L; Burton, Dennis R; Sodroski, Joseph G; Haynes, Barton F; Santra, Sampa

    2015-01-15

    Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques.

  1. Initial founders of captive populations are genetically representative of natural populations in critically endangered dusky gopher frogs, Lithobates sevosus.

    PubMed

    Hinkson, Kristin M; Henry, Natochia L; Hensley, Nina M; Richter, Stephen C

    2016-09-01

    The rapid rate of decline in amphibian populations has urged many researchers and conservationists to establish captive, or ex situ, populations. Such populations are guarded against effects of habitat loss and degradation, and if actively managed, can serve as a reservoir for rare alleles that might be lost in the wild. Without proper management, ex situ population sizes can dwindle and will no longer perform this function. The dusky gopher frog, Lithobates sevosus, is a critically endangered species, imperiled by habitat loss and population isolation. To assist in recovery of the species and prevent further genetic erosion, a captive breeding program was initiated. We investigated how well natural genetic variation was captured within the ex situ population and determined relatedness within each ex situ population. We genotyped individuals from two natural populations and two founding, captive populations to compare metrics of genetic variation and relatedness. The data show the initial founder populations are genetically representative of the natural populations, although variation is low in each, and that relatedness values are similar. Therefore, founding captive populations were successful at capturing genetic variation in the wild. Future research should continue to compare genetic variation of captive and natural populations to monitor efficacy of their management programs. Zoo Biol. 35:378-384, 2016. © 2016 Wiley Periodicals, Inc.

  2. Genetic and morphological evolution following a founder event in the dark-eyed junco, Junco hyemalis thurberi.

    PubMed

    Rasner, C A; Yeh, P; Eggert, L S; Hunt, K E; Woodruff, D S; Price, T D

    2004-03-01

    An isolated population of dark-eyed juncos, Junco hyemalis, became established on the campus of the University of California at San Diego (UCSD), probably in the early 1980s. It now numbers about 70 breeding pairs. Populations across the entire natural range of the subspecies J. h. thurberi are weakly differentiated from each other at five microsatellite loci (FST = 0.01). The UCSD population is significantly different from these populations, the closest of which is 70 km away. It has 88% of the genetic heterozygosity and 63% of the allelic richness of populations in the montane range of the subspecies, consistent with a harmonic mean effective population size of 32 (but with 95% confidence limits from four to > 70) over the eight generations since founding. Results suggest a moderate bottleneck in the early establishment phase but with more than seven effective founders. Individuals in the UCSD population have shorter wings and tails than those in the nearby mountains and a common garden experiment indicates that the morphological differences are genetically based. The moderate effective population size is not sufficient for the observed morphological differences to have evolved as a consequence of genetic drift, indicating a major role for selection subsequent to the founding of the UCSD population.

  3. Genome Wide Association Analysis of a Founder Population Identified TAF3 as a Gene for MCHC in Humans

    PubMed Central

    Pistis, Giorgio; Okonkwo, Shawntel U.; Traglia, Michela; Sala, Cinzia; Shin, So-Youn; Masciullo, Corrado; Buetti, Iwan; Massacane, Roberto; Mangino, Massimo; Thein, Swee-Lay; Spector, Timothy D.; Ganesh, Santhi; Pirastu, Nicola; Gasparini, Paolo; Soranzo, Nicole; Camaschella, Clara; Hart, Daniel; Green, Michael R.; Toniolo, Daniela

    2013-01-01

    The red blood cell related traits are highly heritable but their genetics are poorly defined. Only 5–10% of the total observed variance is explained by the genetic loci found to date, suggesting that additional loci should be searched using approaches alternative to large meta analysis. GWAS (Genome Wide Association Study) for red blood cell traits in a founder population cohort from Northern Italy identified a new locus for mean corpuscular hemoglobin concentration (MCHC) in the TAF3 gene. The association was replicated in two cohorts (rs1887582, P = 4.25E–09). TAF3 encodes a transcription cofactor that participates in core promoter recognition complex, and is involved in zebrafish and mouse erythropoiesis. We show here that TAF3 is required for transcription of the SPTA1 gene, encoding alpha spectrin, one of the proteins that link the plasma membrane to the actin cytoskeleton. Mutations in SPTA1 are responsible for hereditary spherocytosis, a monogenic disorder of MCHC, as well as for the normal MCHC level. Based on our results, we propose that TAF3 is required for normal erythropoiesis in human and that it might have a role in controlling the ratio between hemoglobin (Hb) and cell volume and in the dynamics of RBC maturation in healthy individuals. Finally, TAF3 represents a potential candidate or a modifier gene for disorders of red cell membrane. PMID:23935956

  4. 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.

  5. Mutational analysis in podocin-associated hereditary nephrotic syndrome in Polish patients: founder effect in the Kashubian population.

    PubMed

    Lipska, Beata S; Balasz-Chmielewska, Irena; Morzuch, Lucyna; Wasielewski, Kacper; Vetter, Dominika; Borzecka, Halina; Drozdz, Dorota; Firszt-Adamczyk, Agnieszka; Gacka, Ewa; Jarmolinski, Tomasz; Ksiazek, Joanna; Kuzma-Mroczkowska, Elzbieta; Litwin, Mieczyslaw; Medynska, Anna; Silska, Magdalena; Szczepanska, Maria; Tkaczyk, Marcin; Wasilewska, Anna; Schaefer, Franz; Zurowska, Aleksandra; Limon, Janusz

    2013-08-01

    Hereditary nephrotic syndrome is caused by mutations in a number of different genes, the most common being NPHS2. The aim of the study was to identify the spectrum of NPHS2 mutations in Polish patients with the disease. A total of 141 children with steroid-resistant nephrotic syndrome (SRNS) were enrolled in the study. Mutational analysis included the entire coding sequence and intron boundaries of the NPHS2 gene. Restriction fragment length polymorphism (RFLP) and TaqMan genotyping assay were applied to detect selected NPHS2 sequence variants in 575 population-matched controls. Twenty patients (14 %) had homozygous or compound heterozygous NPHS2 mutations, the most frequent being c.1032delT found in 11 children and p.R138Q found in four patients. Carriers of the c.1032delT allele were exclusively found in the Pomeranian (Kashubian) region, suggesting a founder effect origin. The 14 % NPHS2 gene mutation detection rate is similar to that observed in other populations. The heterogeneity of mutations detected in the studied group confirms the requirement of genetic testing the entire NPHS2 coding sequence in Polish patients, with the exception of Kashubs, who should be initially screened for the c.1032delT deletion.

  6. Compositional assessments of key maize populations: B73 hybrids of the Nested Association Mapping founder lines and diverse landrace inbred lines.

    PubMed

    Venkatesh, Tyamagondlu V; Harrigan, George G; Perez, Tim; Flint-Garcia, Sherry

    2015-06-03

    The present study provides an assessment of the compositional diversity in maize B73 hybrids derived both from the Nested Association Mapping (NAM) founder lines and from a diverse collection of landrace accessions from North and South America. The NAM founders represent a key population of publicly available lines that are used extensively in the maize community to investigate the genetic basis of complex traits. Landraces are also of interest to the maize community as they offer the potential to discover new alleles that could be incorporated into modern maize lines. The compositional analysis of B73 hybrids from the 25 NAM founders and 24 inbred lines derived from landraces included measurements of proximates (protein, fat, ash, and starch), fibers, minerals, amino acids, fatty acids, tocopherols (α-, γ-, and δ-), β-carotene, phytic acid, and raffinose. Grain was harvested from a replicated trial in New York, USA. For each data set (NAM and landrace) canonical discriminant analysis allowed separation of distinct breeding groups (tropical, temperate, flint, mixed/intermediate) within each data set. Overall, results highlighted extensive variation in all composition components assessed for both sets of hybrids. The variation observed for some components within the landraces may therefore be of value for increasing their levels in modern maize lines. The study described here provided significant information on contributions of conventional breeding to crop compositional variation, as well as valuable information on key genetic resources for the maize community in the development of new improved lines.

  7. 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.

  8. Effect of a Founder Event on Variation in the Genetic Sex-Determining System of the Fire Ant Solenopsis Invicta

    PubMed Central

    Ross, K. G.; Vargo, E. L.; Keller, L.; Trager, J. C.

    1993-01-01

    Effects of a recent founder event on genetic diversity in wild populations of the fire ant Solenopsis invicta were studied, with particular attention given to the genetic sex-determining system. Diploid males are far more common relative to haploid males in introduced populations than in native populations of fire ants, and queens that produce diploid males account for a significantly larger proportion of the mated queens in introduced than in native populations. Differences between native and introduced populations in attributes of the mating systems (i.e., queen mating frequency or level of inbreeding) can be excluded as factors contributing to these different levels of diploid male production. Thus, we conclude that diploid males have increased in frequency in introduced populations because of a loss of allelic diversity at the sex-determining locus (loci). This loss of sex alleles has generated a substantial increase in the estimated segregational genetic load associated with production of sterile diploid males in introduced populations over the load in native populations. The loss of allelic diversity in the sex-determining system in introduced S. invicta is paralleled by a loss of electrophoretically detectable rare alleles at protein-encoding loci. Such concordance between these different types of markers is predicted because each of the many sex alleles present in the native populations is expected to be rare. Estimates of expected heterozygosity (H(exp)) based on 76 electrophoretic loci do not differ significantly between the native and introduced fire ant populations, illustrating the lack of sensitivity of this measure for detecting many types of bottlenecks. PMID:8293983

  9. Werner Ernst Reichardt Ph.D: founder of modern computational visual neurophysiology and anti-Nazi resistance fighter.

    PubMed

    Flynn, J T

    1999-01-01

    Werner Ernst Reichardt was born on January 30, 1924 in Berlin and at age 19 was drafted into the Luftwaffe and assigned to an electronic signals section laboratory. He became an active member of a resistance group and supplied radios for the movement in Germany. He emerged from the ashes of the Second World War and dedicated his scientific life to the development of the newborn specialty of biological physics. Following graduation from the Technische Hochschule Charlottenburg, he did a fellowship at CalTech under Max Delbrück. On returning to Germany he joined the Max Planck Institut and later became Director of the Max Planck Institut für Biologische Kybernetik in Tübingen, West Germany. Reichardt was one of the founders of the quantitative study of visually controlled orientation in animals. His work is very nearly unique in its close dialectic between elegant non-linear mathematical theory and quantitative experimental test of their predictions. During the 1950s Reichardt and his collaborators jointly developed an autocorrelation model (i.e. the firing rate of the involved visual neurones is closely correlated with the features of the pattern stimulating them) of how moving patterns are perceived by motion detectors in the visual system of the fly. This was the first mathematical description of a biological abstraction process. His findings apply to vertebrate vision, including motion detection and figure-ground description in human vision. His Max Planck Institute became a world renowned center for the computational approach to information processing by the nervous system. At his retirement party from the Institute he founded, Reichardt died on the evening of September 11th, 1992.

  10. 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. 

  11. Identification of Genetic Variation on the Horse Y Chromosome and the Tracing of Male Founder Lineages in Modern Breeds

    PubMed Central

    Wallner, Barbara; Vogl, Claus; Shukla, Priyank; Burgstaller, Joerg P.; Druml, Thomas; Brem, Gottfried

    2013-01-01

    The paternally inherited Y chromosome displays the population genetic history of males. While modern domestic horses (Equus caballus) exhibit abundant diversity within maternally inherited mitochondrial DNA, no significant Y-chromosomal sequence diversity has been detected. We used high throughput sequencing technology to identify the first polymorphic Y-chromosomal markers useful for tracing paternal lines. The nucleotide variability of the modern horse Y chromosome is extremely low, resulting in six haplotypes (HT), all clearly distinct from the Przewalski horse (E. przewalskii). The most widespread HT1 is ancestral and the other five haplotypes apparently arose on the background of HT1 by mutation or gene conversion after domestication. Two haplotypes (HT2 and HT3) are widely distributed at high frequencies among modern European horse breeds. Using pedigree information, we trace the distribution of Y-haplotype diversity to particular founders. The mutation leading to HT3 occurred in the germline of the famous English Thoroughbred stallion “Eclipse” or his son or grandson and its prevalence demonstrates the influence of this popular paternal line on modern sport horse breeds. The pervasive introgression of Thoroughbred stallions during the last 200 years to refine autochthonous breeds has strongly affected the distribution of Y-chromosomal variation in modern horse breeds and has led to the replacement of autochthonous Y chromosomes. Only a few northern European breeds bear unique variants at high frequencies or fixed within but not shared among breeds. Our Y-chromosomal data complement the well established mtDNA lineages and document the male side of the genetic history of modern horse breeds and breeding practices. PMID:23573227

  12. 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.

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

    PubMed Central

    Cerosaletti, K M; Lange, E; Stringham, H M; Weemaes, C M; Smeets, D; Sölder, B; Belohradsky, B H; Taylor, A M; Karnes, P; Elliott, A; Komatsu, K; Gatti, R A; Boehnke, M; Concannon, P

    1998-01-01

    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. We collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, we 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, we 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. PMID:9634525

  14. 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.

  15. A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New Insights on the SDHC-Related PGL

    PubMed Central

    Grunenwald, Solange; Burnichon, Nelly; Khalifa, Emmanuel; Dumas, Nadine; Binet, Marie-Claire; Nolet, Serge; Gimenez-Roqueplo, Anne-Paule

    2016-01-01

    Background: More than 40% of patients with paragangliomas (PGLs) harbor a germline mutation of the known PGL susceptibility genes, mainly in the SDHB or SDHD genes. Objective: The objective of the study was to characterize the genetic background of the French Canadian (FC) patients with PGLs and provide new clinical and paraclinical insights on SDHC-related PGLs. Methods: Genetic testing has been offered to FC patients affected with PGLs followed up at the adrenal genetics clinic at Centre hospitalier de l'Université de Montréal. After genetic counseling, 29 FC patients consented for PGL genetic testing. Results: Thirteen of 29 patients (44.8%) carried a germline mutation. The same heterozygous nonsense mutation at codon 133 of exon 5 of the SDHC gene (c.397C>T, p.[Arg133Ter]) was found in nine patients, representing 69.2% of the patients having a germline mutation. Seventy percent of these patients had head and neck PGLs. Twenty percent had multiple and 30% had malignant PGLs. We traced back the ascending genealogy of 10 index cases (nine patients from our cohort and one patient referred to us) and found that this mutation was most probably introduced in Nouvelle France by a couple of French settlers who established themselves in the 17th century. Conclusions: We found that 31% of the PGLs in the French Canadian can be explained by the SDHC mutation (c.397C>T, p.[Arg133Ter]). The dominance of the SDHC mutation is unique to the FCs and is most likely due to a French founder effect. SDHC gene analysis should be prioritized in FC patients with PGL. PMID:27700540

  16. Founder of modern cosmonautics

    NASA Astrophysics Data System (ADS)

    Maksimov, A. I.

    2006-12-01

    The basic milestones of the life journey of S.P. Korolev (12.01.1907 14.01.1966), the Designer General of rocket and space systems, are presented. Information on various missiles of the first generation R-1. R-2, R-5, R-7, and R-9, launch vehicles Sputnik, Luna, Molniya, Vostok, Soyuz, and N-1, and also spacecraft designed for various purposes, which were developed under Korolev’s supervision, is given. Korolev’s contribution to the development of rocket engineering and cosmonautics is considered: the reasons for USSR failure in the “Moon race” with the USA are mentioned.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Molecular genetics of achromatopsia in Newfoundland reveal genetic heterogeneity, founder effects and the first cases of Jalili syndrome in North America.

    PubMed

    Doucette, Lance; Green, Jane; Black, Coleman; Schwartzentruber, Jeremy; Johnson, Gordon J; Galutira, Dante; Young, Terry-Lynn

    2013-09-01

    Achromatopsia (ACHM) is a severe retinal disorder characterized by an inability to distinguish colors, impaired visual acuity, photophobia and nystagmus. This rare autosomal recessive disorder of the cone photoreceptors is best known for its increased frequency due to founder effect in the Pingelapese population of the Pacific islands. Sixteen patients from Newfoundland, Canada were sequenced for mutations in the four known achromatopsia genes CNGA3, CNGB3, GNAT2, and PDE6C. The majority (n = 12) of patients were either homozygotes or compound heterozygotes for known achromatopsia alleles, two in CNGB3 (p.T383fsX and p.T296YfsX9) and three in CNGA3 (p.R283Q, p.R427C and p.L527R). Haplotype reconstruction showed that recurrent mutations p.T383fsX and p.L527R were due to a founder effect. Aggregate data from exome sequencing, segregation analysis and archived medical records support a rediagnosis of Jalili syndrome in affected siblings (n = 4) from Family 0094, which to our knowledge is the first family identified with Jalili Syndrome in North America.

  3. The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder.

    PubMed

    Smith, Bradley N; Newhouse, Stephen; Shatunov, Aleksey; Vance, Caroline; Topp, Simon; Johnson, Lauren; Miller, Jack; Lee, Younbok; Troakes, Claire; Scott, Kirsten M; Jones, Ashley; Gray, Ian; Wright, Jamie; Hortobágyi, Tibor; Al-Sarraj, Safa; Rogelj, Boris; Powell, John; Lupton, Michelle; Lovestone, Simon; Sapp, Peter C; Weber, Markus; Nestor, Peter J; Schelhaas, Helenius J; Asbroek, Anneloor Alm Ten; Silani, Vincenzo; Gellera, Cinzia; Taroni, Franco; Ticozzi, Nicola; Van den Berg, Leonard; Veldink, Jan; Van Damme, Phillip; Robberecht, Wim; Shaw, Pamela J; Kirby, Janine; Pall, Hardev; Morrison, Karen E; Morris, Alex; de Belleroche, Jacqueline; Vianney de Jong, J M B; Baas, Frank; Andersen, Peter M; Landers, John; Brown, Robert H; Weale, Michael E; Al-Chalabi, Ammar; Shaw, Christopher E

    2013-01-01

    A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n=1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n=434) and controls (n=856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/-FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/-FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10(-8)). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.

  4. Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes

    SciTech Connect

    Oudet, C.; Lentes-Zengerling, S.; Kretz, C.; Mandel, J.L. ); Mornet, E.; Thomas, F.; Deluchat, C.; Boue, J.; Boue, A. ); Serre, J.L. INSERM U155, Paris ); Tejada, I. )

    1993-02-01

    In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragil X chromosomes. Contrary to observations made in myotonic dystrophy, fragil X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. The authors propose a putative scheme with six founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen. 23 refs., 2 figs., 3 tabs.

  5. Ethnic-Specific WRN Mutations in South Asian Werner Syndrome Patients: Potential Founder Effect in Patients with Indian or Pakistani Ancestry.

    PubMed

    Saha, Bidisha; Lessel, Davor; Nampoothiri, Sheela; Rao, Anuradha S; Hisama, Fuki M; Peter, Dincy; Bennett, Chris; Nürnberg, Gudrun; Nürnberg, Peter; Martin, George M; Kubisch, Christian; Oshima, Junko

    2013-05-01

    Werner syndrome is a rare autosomal recessive disorder characterized by multiple features consistent with accelerated aging. It is caused by mutations in the WRN gene, which encodes a RecQ type helicase. To date, more than 70 disease-causing mutations have been reported. While founder mutations and a corresponding relatively high incidence of WS have been reported in Japan and Sardinia, such mutations have not been previously described among patients of South Asian descent. Here we report two novel WRN mutations in three pedigrees. A homozygous c.561A>G mutation in exon 6 was identified both in a pedigree from Kerala, India and in a British patient of Pakistani ancestry. Although c.561A>G does not alter the corresponding amino acid (p.K187K), it creates a cryptic splice site resulting in a 98bp deletion at the mRNA level (r.557-654del98) followed by a frameshift (p.K187fs). These two cases shared the same haplotype across the WRN gene, and were distinct from another Indian Werner patient with a homozygous stop codon mutation, c.2855 C>A (p.S952*) in exon 24. As the Indian population increases and the awareness of Werner syndrome grows, we anticipate that more cases will be identified with these founder mutations among South Asian Werner syndrome patients.

  6. 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.

  7. Ethnic-specific WRN mutations in South Asian Werner syndrome patients: potential founder effect in patients with Indian or Pakistani ancestry

    PubMed Central

    Saha, Bidisha; Lessel, Davor; Nampoothiri, Sheela; Rao, Anuradha S; Hisama, Fuki M; Peter, Dincy; Bennett, Chris; Nürnberg, Gudrun; Nürnberg, Peter; Martin, George M; Kubisch, Christian; Oshima, Junko

    2013-01-01

    Werner syndrome (WS) is a rare autosomal recessive disorder characterized by multiple features consistent with accelerated aging. It is caused by mutations in the WRN gene, which encodes a RecQ type helicase. To date, more than 70 disease-causing mutations have been reported. While founder mutations and a corresponding relatively high incidence of WS have been reported in Japan and Sardinia, such mutations have not been previously described among patients of South Asian descent. Here, we report two novel WRN mutations in three pedigrees. A homozygous c.561A>G mutation in exon 6 was identified both in a pedigree from Kerala, India and in a British patient of Pakistani ancestry. Although c.561A>G does not alter the corresponding amino acid (p.Lys187), it creates a cryptic splice site resulting in a 98 bp deletion at the mRNA level (r.557_654del98) followed by a frameshift (p.Lys187Trpfs*13). These two cases shared the same haplotype across the WRN gene, and were distinct from another Indian Werner patient with a homozygous stop codon mutation, c.2855 C > A (p.Ser952*), in exon 24. As the Indian population increases and the awareness of WS grows, we anticipate that more cases will be identified with these founder mutations among South Asian WS patients. PMID:23936869

  8. The M53I mutation in CDKN2A is a founder mutation that predominates in melanoma patients with Scottish ancestry.

    PubMed

    Lang, Julie; Hayward, Nicholas; Goldgar, David; Tsao, Hensin; Hogg, David; Palmer, Jane; Stark, Mitchell; Tobias, Edward S; MacKie, Rona

    2007-03-01

    Germline mutations in the tumor suppressor gene CDKN2A have been shown to predispose to cutaneous malignant melanoma. The M53I mutation is the most common CDKN2A mutation identified in Scottish melanoma patients and is also found in a small number of families in other countries. The aim of this study was to determine whether the occurrence of this mutation is due to a common ancestor originating from Scotland, and if so, to estimate how long ago the mutation arose. We examined 18 families carrying the M53I mutation: six from Scotland, five from Canada, four from Australia, and three from America. Haplotypes derived from segregation of seven informative microsatellite markers flanking CDKN2A were constructed in each family. Our findings show that 14 of 18 families carry a common ancestral haplotype on which the mutation arose approximately 88 generations ago (1-LOD-unit support interval 44-198 generations). This haplotype is very rare in controls, which supports the idea that it is a common founder mutation haplotype. The four M53I families that do not share the consensus haplotype may in fact have arisen from the same founder, but this is potentially obscured by presumed replication slippage for some of the microsatellite markers tested.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians

    PubMed Central

    Ebermann, Inga; Koenekoop, Robert K; Lopez, Irma; Bou-Khzam, Lara; Pigeon, Renée; Bolz, Hanno J

    2009-01-01

    Congenital hearing loss affects approximately one child in 1000. About 10% of the deaf population have Usher syndrome (USH). In USH, hearing loss is complicated by retinal degeneration with onset in the first (USH1) or second (USH2) decade. In most populations, diagnostic testing is hampered by a multitude of mutations in nine genes. We have recently shown that in French Canadians from Quebec, USH1 largely results from a single USH1C founder mutation, c.216G>A (‘Acadian allele'). The genetic basis of USH2 in Canadians of French descent, however, has remained elusive. Here, we have investigated nine USH2 families from Quebec and New Brunswick (the former Acadia) by haplotype analyses of the USH2A locus and sequencing of the three known USH2 genes. Seven USH2A mutations were identified in eight patients. One of them, c.4338_4339delCT, accounts for 10 out of 18 disease alleles (55.6%). This mutation has previously been reported in an Acadian USH2 family, and it was found in homozygous state in the three Acadians of our sample. As in the case of c.216G>A (USH1C), a common haplotype is associated with c.4338_4339delCT. With a limited number of molecular tests, it will now be possible in these populations to estimate whether children with congenital hearing impairment of different degrees will develop retinal disease – with important clinical and therapeutic implications. USH2 is the second example that reveals a significant genetic overlap between Quebecois and Acadians: in contrast to current understanding, other genetic disorders present in both populations are likely based on common founder mutations as well. PMID:18665195

  14. Autologous neutralizing antibodies to the transmitted/founder viruses emerge late after simian immunodeficiency virus SIVmac251 infection of rhesus monkeys.

    PubMed

    Yeh, Wendy W; Rahman, Ishita; Hraber, Peter; Coffey, Rory T; Nevidomskyte, Daiva; Giri, Ayush; Asmal, Mohammed; Miljkovic, Svetlana; Daniels, Marcus; Whitney, James B; Keele, Brandon F; Hahn, Beatrice H; Korber, Bette T; Shaw, George M; Seaman, Michael S; Letvin, Norman L

    2010-06-01

    While the simian immunodeficiency virus (SIV)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (HIV-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. In HIV-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. However, the ontogeny of the SIV-specific neutralizing antibody response in mucosally infected animals has not been defined. We characterized the kinetics of the autologous neutralizing antibody response to the transmitted/founder SIVmac251 using a pseudovirion-based TZM-bl cell assay and monitored env sequence evolution using single-genome amplification in four rhesus animals that were infected via intrarectal inoculations. We show that the SIVmac251 founder viruses induced neutralizing antibodies at 5 to 8 months after infection. Despite their slow emergence and low titers, these neutralizing antibodies selected for escape mutants that harbored substitutions and deletions in variable region 1 (V1), V2, and V4 of Env. The neutralizing antibody response was initially focused on V4 at 5 to 8 months after infection and then targeted V1/V2 and V4 by 16 months. These findings reveal a striking delay in the development of neutralizing antibodies in SIVmac-infected animals, thus raising questions concerning the suitability of SIVmac251 as a challenge strain to screen AIDS vaccines that elicit neutralizing antibodies as a means to prevent virus acquisition. They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies.

  15. Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia.

    PubMed

    Gabrikova, Dana; Mistrik, Martin; Bernasovska, Jarmila; Bozikova, Alexandra; Behulova, Regina; Tothova, Iveta; Macekova, Sona

    2013-11-01

    Autosomal recessive forms of Charcot-Marie-Tooth disease (CMT) account for less than 10 % of all CMT cases, but are more frequent in the populations with a high rate of consanguinity. Roma (Gypsies) are a transnational minority with an estimated population of 10 to 14 million, in which a high degree of consanguineous marriages is a generally known fact. Similar to the other genetically isolated founder populations, the Roma harbour a number of unique or rare autosomal recessive disorders, caused by "private" founder mutations. There are three subtypes of autosomal recessive CMT with mutations private to the Roma population: CMT4C, CMT4D and CMT4G. We report on the molecular examination of four families of Roma origin in Slovakia with early-onset demyelinating neuropathy and autosomal recessive inheritance. We detected mutation p.R148X (g.631C>T) in the NDRG1 (NM_006096.3) gene in two families and mutation g.9712G>C in the HK1 (NM_033498) gene in the other two families. These mutations cause CMT4D and CMT4G, respectively. The success of molecular genetic analysis in all families confirms that autosomal recessive forms of CMT caused by mutations on the NDRG1 and HK1 genes are common causes of inherited neuropathies among Slovak Roma. Providing genetic analysis of these genes for patients with Roma origin as a common part of diagnostic procedure would contribute to a better rate of diagnosed cases of demyelinating neuropathy in Slovakia and in other countries with a Roma minority.

  16. Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma.

    PubMed

    Schwabova, Jaroslava; Brozkova, Dana Safka; Petrak, Borivoj; Mojzisova, Mahulena; Pavlickova, Klara; Haberlova, Jana; Mrazkova, Lenka; Hedvicakova, Petra; Hornofova, Ludmila; Kaluzova, Marie; Fencl, Filip; Krutova, Marcela; Zamecnik, Josef; Seeman, Pavel

    2013-12-01

    Pontocerebellar hypoplasia type 1 (PCH1) is characterized by cerebellar and anterior horn motor neuron degeneration and loss, signs of spinal muscular atrophy plus. Patients manifest severe perinatal weakness, hypotonia, and respiratory insufficiency, causing death frequently before the age of 1 year. Recently, causative mutations in EXOSC3 were reported in a majority of PCH1 patients, but the detailed clinical phenotype caused by EXOSC3 mutations, genotype-phenotype correlations, and prevalent mutations in specific ethnic groups is not yet known. Three unrelated Czech Roma patients with PCH1 were investigated clinically, electrophysiologically, neuroradiologically, and neuropathologically (patients 1 and 2). The entire coding region of the EXOSC3 gene, including the adjacent intron sequences, was sequenced in all three patients. The same mutation c.92G→C, p.G31A in EXOSC3 was found in all three affected patients in homozygous state and in heterozygous state in the parents from two of the families. Haplotype analysis with four flanking microsatellite markers showed identical haplotype in 9 out of 11 haplotypes carrying the c.92G→C, p.G31A mutation. Furthermore, four heterozygotes for this mutation were found in anonymous DNA samples from 90 unrelated Roma individuals. All four of these samples shared the same haplotype. No heterozygous sample was found among 120 anonymous DNA samples from Czech non-Roma individuals with no familial relation. It may therefore be concluded that EXOSC3 c.92G→C, p.G31A mutation is a founder mutation with high prevalence among the Czech Roma causing a similar and particularly severe phenotype of PCH1. These observations from the Czech Roma may have consequences also for other Roma from other countries. PCH1 caused by EXOSC3 founder mutation c.92G→C, p.G31A extends the list of autosomal recessive disorders rare among the general population but more frequent among Roma at least in the Czech Republic.

  17. The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents

    PubMed Central

    STRAY-PEDERSEN, A; JÓNSSON, T; HEIBERG, A; LINDMAN, C R; WIDING, E; AABERGE, I S; BORRESEN-DALE, A L; ABRAHAMSEN, T G

    2004-01-01

    Eleven Norwegian patients (aged 2–33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0·23 (0·05–0·41) g/l versus 0·91 (0·58–1·26) g/l in the other patients (P = 0·002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0·9 (0·4–1·4) U/ml, while normal levels were found in their parents 11·1 (8·7–13·4) U/ml (P < 0·001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0·85, P = 0·001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23–64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype. PMID:15196260

  18. 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.

  19. 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).

  20. 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

  1. Adoptive Transfer of Engineered Rhesus Simian Immunodeficiency Virus-Specific CD8+ T Cells Reduces the Number of Transmitted/Founder Viruses Established in Rhesus Macaques.

    PubMed

    Ayala, Victor I; Trivett, Matthew T; Barsov, Eugene V; Jain, Sumiti; Piatak, Michael; Trubey, Charles M; Alvord, W Gregory; Chertova, Elena; Roser, James D; Smedley, Jeremy; Komin, Alexander; Keele, Brandon F; Ohlen, Claes; Ott, David E

    2016-11-01

    AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4(+) T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus.

  2. Autologous Neutralizing Antibodies to the Transmitted/Founder Viruses Emerge Late after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys▿

    PubMed Central

    Yeh, Wendy W.; Rahman, Ishita; Hraber, Peter; Coffey, Rory T.; Nevidomskyte, Daiva; Giri, Ayush; Asmal, Mohammed; Miljkovic, Svetlana; Daniels, Marcus; Whitney, James B.; Keele, Brandon F.; Hahn, Beatrice H.; Korber, Bette T.; Shaw, George M.; Seaman, Michael S.; Letvin, Norman L.

    2010-01-01

    While the simian immunodeficiency virus (SIV)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (HIV-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. In HIV-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. However, the ontogeny of the SIV-specific neutralizing antibody response in mucosally infected animals has not been defined. We characterized the kinetics of the autologous neutralizing antibody response to the transmitted/founder SIVmac251 using a pseudovirion-based TZM-bl cell assay and monitored env sequence evolution using single-genome amplification in four rhesus animals that were infected via intrarectal inoculations. We show that the SIVmac251 founder viruses induced neutralizing antibodies at 5 to 8 months after infection. Despite their slow emergence and low titers, these neutralizing antibodies selected for escape mutants that harbored substitutions and deletions in variable region 1 (V1), V2, and V4 of Env. The neutralizing antibody response was initially focused on V4 at 5 to 8 months after infection and then targeted V1/V2 and V4 by 16 months. These findings reveal a striking delay in the development of neutralizing antibodies in SIVmac-infected animals, thus raising questions concerning the suitability of SIVmac251 as a challenge strain to screen AIDS vaccines that elicit neutralizing antibodies as a means to prevent virus acquisition. They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies. PMID:20357097

  3. Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2

    PubMed Central

    2014-01-01

    Background Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering > 90% of cases, are KCNQ1, KCNH2 and SCN5A. Methods We describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2. Results Twenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 “unrelated” families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of < 1:1000. Conclusion The genetic etiology of LQTS in Denmark is similar to that found in other populations. A large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis. PMID:24606995

  4. Fifty-five years (1955-2010) of the Coagulation Section at Laboratory of Hematology, Sestre milosrdnice University Hospital, and its founder, hematologist Ljubomir Popović.

    PubMed

    Stancić, Vladimir; Stancić, Nevenka; Vucelić, Vesna; Lang, Nada; Grbac, Ljiljana

    2011-09-01

    The Coagulation Section at Laboratory of Hematology, Sestre milosrdnice University Hospital, Zagreb, was founded in 1955 by Ljubomir Popović, hematologist and assistant at School of Medicine, University of Zagreb, in cooperation with hard-working laboratory technicians. Apart from papers on hematologic neoplasms, plasmacytoma and lymphoma, Ljubomir Popović published a number of papers in the field of anticoagulant therapy with heparin and oral anticoagulants, some of which are also in use today. After Ljubomir Popović left the Hospital in 1964, the Laboratory was run by Professor Nedjeljko Milić, head of the newly founded Division of Hematology. In 1968, the management of the Laboratory of Hematology was taken over by Biserka Raić, MS, medical biochemist, until her retirement in 2007. Great development in morphological and cytometric studies of blood and blood cells has been paralleled by continuous progress and almost dominating activities in the diagnosis of hemostasis disorders. In the 1970s, Marko Koprcina, hematologist, and Biserka Raić introduced the then latest tests in practice at all Hospital departments. In that golden age of the Coagulation Section, M. Koprcina, B. Raić and their associates transferred their knowledge to all colleagues in the Hospital. Through that collaboration, high standards in the diagnosis of hemostasis disorders were achieved, from which the currently high level of clinical knowledge about coagulation disorders and their treatment has derived, making Sestre milosrdnice University Hospital one of the leading hospitals in this field in the country. By describing development of the Coagulation Section and the life of its founder Ljubomir Popović, the authors tried to provide an answer to the following question: can today's clinicians still have a deciding role in laboratory development, considering that assessments of different phenomena are always initiated by an interested clinician who is trying to interpret and understand

  5. BRCA Genetic Screening in Middle Eastern and North African: Mutational Spectrum and Founder BRCA1 Mutation (c.798_799delTT) in North African

    PubMed Central

    Laraqui, Abdelilah; Uhrhammer, Nancy; EL Rhaffouli, Hicham; Sekhsokh, Yassine; Lahlou-Amine, Idriss; Bajjou, Tahar; Hilali, Farida; El Baghdadi, Jamila; Al Bouzidi, Abderrahmane; Bakri, Youssef; Amzazi, Said; Bignon, Yves-Jean

    2015-01-01

    Background. The contribution of BRCA1 mutations to both hereditary and sporadic breast and ovarian cancer (HBOC) has not yet been thoroughly investigated in MENA. Methods. To establish the knowledge about BRCA1 mutations and their correlation with the clinical aspect in diagnosed cases of HBOC in MENA populations. A systematic review of studies examining BRCA1 in BC women in Cyprus, Jordan, Egypt, Lebanon, Morocco, Algeria, and Tunisia was conducted. Results. Thirteen relevant references were identified, including ten studies which performed DNA sequencing of all BRCA1 exons. For the latter, 31 mutations were detected in 57 of the 547 patients ascertained. Familial history of BC was present in 388 (71%) patients, of whom 50 were mutation carriers. c.798_799delTT was identified in 11 North African families, accounting for 22% of total identified BRCA1 mutations, suggesting a founder allele. A broad spectrum of other mutations including c.68_69delAG, c.181T>G, c.5095C>T, and c.5266dupC, as well as sequence of unclassified variants and polymorphisms, was also detected. Conclusion. The knowledge of genetic structure of BRCA1 in MENA should contribute to the assessment of the necessity of preventive programs for mutation carriers and clinical management. The high prevalence of BC and the presence of frequent mutations of the BRCA1 gene emphasize the need for improving screening programs and individual testing/counseling. PMID:25814778

  6. Haplotype and AGG interspersion analysis of FMR1 alleles in a Croatian population: no founder effect detected in patients with fragile X syndrome.

    PubMed

    Dokić, H; Barisić, I; Culić, V; Lozić, B; Hećimović, S

    2008-10-01

    Several studies have suggested that fragile X syndrome (FRAXA), the most common inherited form of mental retardation, originated from a limited number of founder chromosomes. The aim of this study is to assess the genetic origin of fragile X syndrome in a Croatian population. We performed a haplotype analysis of the polymorphic loci DXS548 and FRAXAC1 in 18 unrelated fragile X and 56 control chromosomes. The AGG interspersion pattern of the FMR1 CGG repeat region was analyzed by sequencing. This is the first report on haplotype and AGG interspersion analysis of the fragile X syndrome gene in a Croatian population-the only eastern European population of Slavic origin analyzed so far. Our findings are intriguing, because they show a distinct distribution of the DXS548 and FRAXAC1 alleles in our fragile X population compared to other European fragile X populations. The DXS548/FRAXAC1 haplotype 194/154 (7-3), which is common among normal populations, was found to be the most frequent haplotype in our fragile X population as well. The AGG interspersion analysis indicated that AGG loss rather than haplotype may determine FMR1 allele instability. Our results suggest that no common ancestral X chromosome is associated with fragile X syndrome in the Croatian population studied. Further analysis of the origin of fragile X syndrome among other Slavic populations will be necessary to better define its eastern European distribution.

  7. 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.

  8. 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.

  9. 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

  10. Effect of multiple endocrine neoplasia type 1 (MEN1) gene mutations on premature mortality in familial MEN1 syndrome with founder mutations.

    PubMed

    Ebeling, T; Vierimaa, O; Kytölä, S; Leisti, J; Salmela, P I

    2004-07-01

    Estimation of mortality and the natural course of a disease is usually based on information of carefully studied individuals with or at risk for a specific disease. Genealogical information has rarely been accurate enough for such studies. With the help of church records and multiple endocrine neoplasia type 1 (MEN1) family information of the two founder MEN1 mutations in Northern Finland (1466del12 and 1657insC), we could trace back common ancestors born in the beginning of the 1700s (1466del12) and approximately 1850 (1657insC) and find 67 probable gene carriers born between 1728 and 1929, which were identified among their offspring. Information was gathered from 34 obligatory MEN1 gene carriers and 31 spouses. The mean age (+/- sd) of death of affected males (n = 16) was 61.1 +/- 12.0 yr vs. 65.8 +/- 15.3 yr for unaffected males (n = 16) and for affected females (n = 16) was 67.2 +/- 10.7 yr vs. 67.7 +/- 14.7 yr for unaffected females (n = 13). The ages of death of the obligatory heterozygotes did not differ from that of the spouses in sex groups or from the sex-matched life expectancy estimates derived from Finnish national statistics. Causes of death differed significantly between female probands and spouses. In conclusion, obligatory MEN1 gene carrier status did not show a harmful effect on survival in this retrospective analysis tracing back to almost 300 yr.

  11. Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G₂arrest and cell apoptosis.

    PubMed

    Jianyuan, Zhao; Jiwei, Ding; Zeyun, Mi; Jinming, Zhou; Tao, Wei; Shan, Cen

    2015-05-01

    In the event of acute infection, only a few HIV-1 viral variants can establish the initial productive clinical infection, and these viral variants are known as transmitted/founder viruses (T/F viruses). As one of the accessory proteins of HIV-1, viral protein R (Vpr) plays an important role in viral replication. Therefore, the characterization of T/F virus Vpr is beneficial to understand how virus replicates in a new host. In this study, flow cytometry was used to analyze the effect of G₂arrest and cell apoptosis induced by the T/F virus Vpr and the chronic strain MJ4 Vpr. The results showed that the ability of T/F virus ZM246 Vpr and ZM247 Vpr inducing G₂arrest and cell apoptosis are more potent than the MJ4 Vpr. The comparison of protein sequences indicated that the amino acids of 77, 85 and 94 contain high freqency mutations, suggesting that these sites may be involved in inducing G₂arrest and cell apoptosis. Taken together, our work suggests that in acute infections, T/F viruses increase the capacity of G₂arrest and cell apoptosis and promote viral replication and transmission in a new host by Vpr genetic mutation.

  12. A novel 3-bp deletion in the PANK2 gene of Dutch patients with pantothenate kinase-associated neurodegeneration: evidence for a founder effect.

    PubMed

    Rump, P; Lemmink, H H; Verschuuren-Bemelmans, C C; Grootscholten, P M; Fock, J M; Hayflick, S J; Westaway, S K; Vos, Y J; van Essen, A J

    2005-12-01

    Mutation analysis was performed in four apparently unrelated Dutch families with pantothenate kinase-associated neurodegeneration, formerly known as Hallervorden-Spatz syndrome. A novel 3-bp deletion encompassing the nucleotides GAG at positions 1,142 to 1,144 of exon 5 of the PANK2 gene was found in all patients. One patient was compound heterozygous; she also carried a novel nonsense mutation (Ser68Stop). The other patients were homozygous for the 1142_1144delGAG mutation. The 1142_1144delGAG mutation was also found in a German patient of unknown descent. We used polymorphic microsatellite markers flanking the PANK2 gene (spanning a region of approximately 8 cM) for haplotype analyses in all these families. A conserved haplotype of 1.5 cM was found for the 1142_1144delGAG mutation carriers. All the Dutch families originated from the same geographical region within the Netherlands. The results indicate a founder effect and suggest that the 1142_1144delGAG mutation probably originated from one common ancestor. It was estimated that this mutation arose at the beginning of the ninth century, approximately 38 generations ago.

  13. The History of the Foundation of the Iranian National Blood Transfusion Service in 1974 and the Biography of its Founder; Professor Fereydoun Ala.

    PubMed

    Azizi, Mohammad Hossein; Nayernouri, Touraj; Bahadori, Moslem

    2015-06-01

    The history of early attempts of blood transfusion in Iran traces back to the 1940s; however, around three decades later in 1974, the Iranian National Blood Transfusion Service (Sazeman-e Melli-e Enteqal-e Khun-e Iran) was founded by the outstanding hematologist, Professor Fereydoun Ala. The main goals of this centralized organization were to collect blood from healthy voluntary donors, to screen the donated blood and to provide various safe blood products based on scientific and ethical standards. In due course, a new era of blood transfusion service in Iran had begun to such a degree that after more than four decades of its activity, it is now considered the best-developed blood service in the eastern Mediterranean region. Here, a brief historical account of the early blood transfusion efforts and the establishment of the modern Iranian National Blood Transfusion Service in Iran is discussed in addition to the life and career of its founder and first director, Professor Fereydoun Ala.

  14. Genetically heterogeneous selective intestinal malabsorption of vitamin B12: founder effects, consanguinity, and high clinical awareness explain aggregations in Scandinavia and the Middle East.

    PubMed

    Tanner, Stephan M; Li, Zhongyuan; Bisson, Ryan; Acar, Ceren; Oner, Cihan; Oner, Reyhan; Cetin, Mualla; Abdelaal, Mohamed A; Ismail, Essam A; Lissens, Willy; Krahe, Ralf; Broch, Harald; Gräsbeck, Ralph; de la Chapelle, Albert

    2004-04-01

    Selective intestinal malabsorption of vitamin B(12) causing juvenile megaloblastic anemia (MGA; MIM# 261100) is a recessively inherited disorder that is believed to be rare except for notable clusters of cases in Finland, Norway, and the Eastern Mediterranean region. The disease can be caused by mutations in either the cubilin (CUBN; MGA1; MIM# 602997) or the amnionless (AMN; MIM# 605799) gene. To explain the peculiar geographical distribution, we hypothesized that mutations in one of the genes would mainly be responsible for the disease in Scandinavia, and mutations in the other gene in the Mediterranean region. We studied 42 sibships and found all cases in Finland to be due to CUBN (three different mutations) and all cases in Norway to be due to AMN (two different mutations), while in Turkey, Israel, and Saudi Arabia, there were two different AMN mutations and three different CUBN mutations. Haplotype evidence excluded both CUBN and AMN conclusively in five families and tentatively in three families, suggesting the presence of at least one more gene locus that can cause MGA. We conclude that the Scandinavian cases are typical examples of enrichment by founder effects, while in the Mediterranean region high degrees of consanguinity expose rare mutations in both genes. We suggest that in both regions, physician awareness of this disease causes it to be more readily diagnosed than elsewhere; thus, it may well be more common worldwide than previously thought.

  15. AmericaPlex26: A SNaPshot Multiplex System for Genotyping the Main Human Mitochondrial Founder Lineages of the Americas

    PubMed Central

    Coutinho, Alexandra; Valverde, Guido; Fehren-Schmitz, Lars; Cooper, Alan; Barreto Romero, Maria Inés; Espinoza, Isabel Flores; Llamas, Bastien; Haak, Wolfgang

    2014-01-01

    Phylogeographic studies have described a reduced genetic diversity in Native American populations, indicative of one or more bottleneck events during the peopling and prehistory of the Americas. Classical sequencing approaches targeting the mitochondrial diversity have reported the presence of five major haplogroups, namely A, B, C, D and X, whereas the advent of complete mitochondrial genome sequencing has recently refined the number of founder lineages within the given diversity to 15 sub-haplogroups. We developed and optimized a SNaPshot assay to study the mitochondrial diversity in pre-Columbian Native American populations by simultaneous typing of 26 single nucleotide polymorphisms (SNPs) characterising Native American sub-haplogroups. Our assay proved to be highly sensitive with respect to starting concentrations of target DNA and could be applied successfully to a range of ancient human skeletal material from South America from various time periods. The AmericaPlex26 is a powerful assay with enhanced phylogenetic resolution that allows time- and cost-efficient mitochondrial DNA sub-typing from valuable ancient specimens. It can be applied in addition or alternative to standard sequencing of the D-loop region in forensics, ancestry testing, and population studies, or where full-resolution mitochondrial genome sequencing is not feasible. PMID:24671218

  16. Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene.

    PubMed

    Cavaco, Branca M; Guerra, Laura; Bradley, Karin J; Carvalho, Davide; Harding, Brian; Oliveira, Amélia; Santos, Maria-Amparo; Sobrinho, Luís G; Thakker, Rajesh V; Leite, Valeriano

    2004-04-01

    The hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by the occurrence of parathyroid tumors and ossifying jaw fibromas. The gene causing HPT-JT, HRPT2, is located on chromosome 1q31.2 and consists of 17 exons that encode a 531-amino acid protein, designated parafibromin. We recently identified six Roma families in Portugal with 56 members (11 affected and 45 asymptomatic), who had the HPT-JT syndrome. We postulated that they may have a common ancestor and that the HPT-JT syndrome may be due to a mutation of the HRPT2 gene. Haplotype analysis using 14 chromosome 1q24-q32 polymorphic markers showed that the 11 affected individuals shared a common haplotype defined by seven markers that spanned an approximately 12.5-cM region, flanked centromerically by D1S202 and telomerically by D1S306. DNA sequence analysis identified a 2-bp (TG or GT) frameshift deletion in exon 8, which predicts a truncated parafibromin protein, in all 11 affected individuals. This mutation was also found in 19 unaffected individuals (age range, 12-74 yr) who shared the affected haplotype, suggesting a low age-related penetrance for HPT-JT in these families. Thus, the HPT-JT syndrome in six Roma families from Portugal is due to a novel founder mutation in the HRPT2 gene.

  17. Transmission of Multiple HIV-1 Subtype C Transmitted/founder Viruses into the Same Recipients Was not Determined by Modest Phenotypic Differences

    PubMed Central

    Song, Hongshuo; Hora, Bhavna; Giorgi, Elena E.; Kumar, Amit; Cai, Fangping; Bhattacharya, Tanmoy; Perelson, Alan S.; Gao, Feng

    2016-01-01

    A severe bottleneck exists during HIV-1 mucosal transmission. However, viral properties that determine HIV-1 transmissibility are not fully elucidated. We identified multiple transmitted/founder (T/F) viruses in six HIV-1-infected subjects by analyzing whole genome sequences. Comparison of biological phenotypes of different T/F viruses from the same individual allowed us to more precisely identify critical determinants for viral transmissibility since they were transmitted under similar conditions. All T/F viruses used coreceptor CCR5, while no T/F viruses used CXCR4 or GPR15. However, the efficiency for different T/F viruses from the same individual to use CCR5 was significantly variable, and the differences were even more significant for usage of coreceptors FPRL1, CCR3 and APJ. Resistance to IFN-α was also different between T/F viruses in 2 of 3 individuals. The relative fitness between T/F viruses from the same subject was highly variable (2–6%). Importantly, the levels of coreceptor usage efficiency, resistance to IFN-α and viral fitness were not associated with proportions of T/F viruses in each individual during acute infection. Our results show that the modest but significant differences in coreceptor usage efficiency, IFN-α sensitivity and viral fitness each alone may not play a critical role in HIV-1 transmission. PMID:27909304

  18. 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

  19. 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

  20. Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection

    PubMed Central

    Lopker, Michael J.; Del Prete, Gregory Q.; Estes, Jacob D.; Li, Hui; Reid, Carolyn; Newman, Laura; Lipkey, Leslie; Camus, Celine; Easlick, Juliet L.; Wang, Shuyi; Decker, Julie M.; Bar, Katharine J.; Learn, Gerald; Pal, Ranajit; Weiss, Deborah E.; Hahn, Beatrice H.; Lifson, Jeffrey D.; Shaw, George M.

    2016-01-01

    ABSTRACT Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in nonhuman primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single-genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competent in vitro, with replication kinetics similar to those of the widely used chronic-infection-derived IMCs SIVmac239 and SIVsmE543. Phenotypically, the new T/F virus strains exhibited a range of neutralization sensitivity profiles. Four T/F virus strains were inoculated into rhesus macaques, and each exhibited typical SIV replication kinetics. The SIVsm T/F viruses were sensitive to TRIM5α restriction. All T/F viruses were pathogenic in rhesus macaques, resulting in progressive CD4+ T cell loss in gastrointestinal tissues, peripheral blood, and lymphatic tissues. The animals developed pathological immune activation; lymphoid tissue damage, including fibrosis; and clinically significant immunodeficiency leading to AIDS-defining clinical endpoints. These T/F clones represent a new molecular platform for the analysis of virus transmission and immunopathogenesis and for the generation of novel “bar-coded” challenge viruses and next-generation simian-human immunodeficiency viruses that may advance the HIV/AIDS vaccine agenda. IMPORTANCE Nonhuman primate research has relied on only a few

  1. Founder Effect of a c.828+3A>T Splice Site Mutation in Peripherin 2 (PRPH2) Causing Autosomal Dominant Retinal Dystrophies

    PubMed Central

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

    2015-01-01

    single-nucleotide polymorphism) in exon 3 of PRPH2, suggesting this mutation is from a common ancestor and is a founder mutation. It has a prevalence of 2% in families diagnosed as having autosomal dominant retinitis pigmentosa and 10% in families with variable clinical diagnosis of pattern, macular, and retinal dystrophies. Individuals with the c.828+3A>T mutation expressed a PRPH2 transcript not found in control participants and that was consistent with abnormal splicing. Conclusions and Relevance The PRPH2 c.828+3A>T splice site mutation is a frequent cause of inherited retinal dystrophies and is owing to the founder effect. The likely cause of disease is the missplicing of the PRPH2 message that results in a truncated protein product. Identifying the genetic etiology assists in more accurate management and possible future therapeutic options. PMID:25675413

  2. 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

  3. The Genomic Landscape of TP53 and p53 Annotated High Grade Ovarian Serous Carcinomas from a Defined Founder Population Associated with Patient Outcome

    PubMed Central

    Wojnarowicz, Paulina M.; Oros, Kathleen Klein; Quinn, Michael C. J.; Arcand, Suzanna L.; Gambaro, Karen; Madore, Jason; Birch, Ashley H.; de Ladurantaye, Manon; Rahimi, Kurosh; Provencher, Diane M.; Mes-Masson, Anne-Marie; Greenwood, Celia M. T.; Tonin, Patricia N.

    2012-01-01

    High-grade ovarian serous carcinomas (HGSC) are characterized by TP53 mutations and non-random patterns of chromosomal anomalies, where the nature of the TP53 mutation may correlate with clinical outcome. However, the frequency of common somatic genomic events occurring in HGSCs from demographically defined populations has not been explored. Whole genome SNP array, and TP53 mutation, gene and protein expression analyses were assessed in 87 confirmed HGSC samples with clinical correlates from French Canadians, a population exhibiting strong founder effects, and results were compared with independent reports describing similar analyses from unselected populations. TP53 mutations were identified in 91% of HGSCs. Anomalies observed in more than 50% of TP53 mutation-positive HGSCs involved gains of 3q, 8q and 20q, and losses of 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 22q and Xp. Nearly 400 regions of non-overlapping amplification or deletion were identified, where 178 amplifications and 98 deletions involved known genes. The subgroup expressing mutant p53 protein exhibited significantly prolonged overall and disease-free survival as compared with the p53 protein null subgroup. Interestingly, a comparative analysis of genomic landscapes revealed a significant enrichment of gains involving 1q, 8q, and 12p intervals in the subgroup expressing mutant p53 protein as compared with the p53 protein null subgroup. Although the findings show that the frequency of TP53 mutations and the genomic landscapes observed in French Canadian samples were similar to those reported for samples from unselected populations, there were differences in the magnitude of global gains/losses of specific chromosomal arms and in the spectrum of amplifications and deletions involving focal regions in individual samples. The findings from our comparative genomic analyses also support the notion that there may be biological differences between HGSCs that could be related to the nature of the TP53 mutation

  4. 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.

  5. 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.

  6. Reduced potency and incomplete neutralization of broadly neutralizing antibodies against cell-to-cell transmission of HIV-1 with transmitted founder Envs.

    PubMed

    Li, Hongru; Zony, Chati; Chen, Ping; Chen, Benjamin K

    2017-02-01

    Broadly neutralizing antibodies (bNAbs) have been isolated from HIV-1 patients and can potently block infection of a wide spectrum of HIV-1 subtypes. These antibodies define common epitopes shared by many viral isolates. While bNAbs potently antagonize infection with cell-free virus, inhibition of HIV-1 transmission from infected to uninfected CD4(+) T cells through virological synapses (VS), has been found to require greater amounts of antibody. In this study, we examined two well-studied molecular clones and two transmitted founder (T/F) viruses for their sensitivities to a panel of bNAbs in cell-free and cell-to-cell infection assays. We observed a relative resistance of cell-to-cell transmission to antibody neutralization that is reflected not only by reductions of antibody potency, but also by decreases in maximum neutralization capacity relative to cell-free infections. BNAbs targeting different epitopes exhibited incomplete neutralization against cell-associated virus with T/F Envs, which was not observed with cell-free form of the same virus. We further identified the membrane proximal internal tyrosine-based sorting motif as a determinant that can affect the incomplete neutralization of these T/F clones in cell-to-cell infection. These findings indicate that the signal that affects surface expression and/or internalization of Env from the plasma membrane can modulate the presentation of neutralizing epitopes on infected cells. These findings highlight that a fraction of virus can escape from high concentrations of antibody through cell-to-cell infection while maintaining sensitivity to neutralization in cell-free infection. The ability to fully inhibit cell-to-cell transmission may represent an important consideration in development of antibodies for treatment or prophylaxis.

  7. 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

  8. 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

    Ancot, Frédéric; Arcand, Suzanna L; Mes-Masson, Anne-Marie; Provencher, Diane M; Tonin, Patricia N

    2015-06-01

    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.

  9. Haplotype variation in a mitochondrial tandem repeat of Norway spruce (Picea abies) populations suggests a serious founder effect during postglacial re-colonization of the western Alps.

    PubMed

    Gugerli, F; Sperisen, C; Büchler, U; Magni, F; Geburek, T; Jeandroz, S; Senn, J

    2001-05-01

    Populations from 13 elevational transects of Norway spruce [Picea abies (L.) Karst] across the Alpine range were sampled to elucidate the geographical pattern of genetic variation in relation to postglacial re-colonization and to study elevational effects on haplotypic diversity. We assessed fragment length variation in a tandem repeat region of the mitochondrial (mt) nad1 intron 2. This maternally inherited genetic marker is suited to infer migration as it is dispersed by seed only. A total of 10 haplotypes was found, most of which were due to repeat copy number variation. An analysis of molecular variance (amova) showed that overall population differentiation was high (F(ST)=0.41), and it revealed a significant differentiation between monomorphic western and moderately to highly variable eastern Alpine populations. This phylogeographic pattern may be explained by a founder effect during postglacial re-colonization. An early arriving haplotype, assumed to originate from a western Carpathian refugium, could expand into suitable habitats, reducing the chances for establishment of subsequently arriving haplotypes. On the other hand, the high variation in populations within an Italian transect of the south-eastern Alps may be the consequence of merging migration pathways from and close distance to putative glacial refugia, most likely those assumed in the Carpathian mountains and on the Balkan peninsula or possibly in the central plains of Italy. An effect of elevation on haplotypic diversity was not evident, though a low, but significant, partition of total genetic variation was attributed to among-population variation in one Italian transect. Various factors, such as vertical seed dispersal and forest management, may account for blurring an otherwise established pattern of genetic variation on a small geographical scale.

  10. Identification and surveillance of 19 Lynch syndrome families in southern Italy: report of six novel germline mutations and a common founder mutation.

    PubMed

    Lastella, Patrizia; Patruno, Margherita; Forte, Giovanna; Montanaro, Alba; Di Gregorio, Carmela; Sabbà, Carlo; Suppressa, Patrizia; Piepoli, Adalgisa; Panza, Anna; Andriulli, Angelo; Resta, Nicoletta; Stella, Alessandro

    2011-06-01

    Lynch syndrome (LS), or hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant condition responsible for early onset cancer mostly in the colonrectum and endometrium as well as in other organ sites. Lynch syndrome is caused by germline mutations in mismatch repair genes, prevalently in hMSH2, hMLH1, and less frequently in hMSH6 and hPMS2. Twenty-nine non-related index cases with colorectal cancer (CRC) were collected from a region in southeast Italy (Apulia). Among this set of patients, fifteen fulfilled the Amsterdam criteria II. The presence of tumor microsatellite instability (MSI) was assessed in all index cases and 19 (15 AC+/4 AC-) were classified as MSI-H. Mutation analysis performed on all patients, identified 15 pathogenic mutations in hMLH1 and 4 in hMSH2. 4/15 mutations in hMLH1 and 2/4 hMSH2 mutations have not been previously reported. Three previously reported mutations were further investigated for the possibility of a common founder effect. Genetic counseling was offered to all probands and extended to 183 relatives after molecular testing and 85 (46%) mutation carriers were identified. Eighty mutation carriers underwent an accurate clinical and instrumental surveillance protocol. Our results confirm that the identification of LS patients based exclusively on family history may miss patients carrying germline mutations in the MMR genes. Moreover, our results demonstrated that molecular screening and subsequent instrumental surveillance are very effective in identifying CRCs at earlier stages and reducing the number of deaths from secondary cancers in HNPCC patients.

  11. Initial HIV-1 antigen-specific CD8+ T cells in acute HIV-1 infection inhibit transmitted/founder virus replication.

    PubMed

    Freel, Stephanie A; Picking, Ralph A; Ferrari, Guido; Ding, Haitao; Ochsenbauer, Christina; Kappes, John C; Kirchherr, Jennifer L; Soderberg, Kelly A; Weinhold, Kent J; Cunningham, Coleen K; Denny, Thomas N; Crump, John A; Cohen, Myron S; McMichael, Andrew J; Haynes, Barton F; Tomaras, Georgia D

    2012-06-01

    CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8(+) T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8(+) responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8(+) T cells during AHI. Autologous and heterologous CD8(+) T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8(+) T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8(+) antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8(+)-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8(+) T cell-mediated inhibition of virus replication. CD8(+) T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.

  12. 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

  13. Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number.

    PubMed Central

    Parsons, D W; McAndrew, P E; Iannaccone, S T; Mendell, J R; Burghes, A H; Prior, T W

    1998-01-01

    The autosomal recessive neuromuscular disorder proximal spinal muscular atrophy (SMA) is caused by the loss or mutation of the survival motor neuron (SMN) gene, which exists in two nearly identical copies, telomeric SMN (telSMN) and centromeric SMN (cenSMN). Exon 7 of the telSMN gene is homozygously absent in approximately 95% of SMA patients, whereas loss of cenSMN does not cause SMA. We searched for other telSMN mutations among 23 SMA compound heterozygotes, using heteroduplex analysis. We identified telSMN mutations in 11 of these unrelated SMA-like individuals who carry a single copy of telSMN: these include two frameshift mutations (800ins11 and 542delGT) and three missense mutations (A2G, S262I, and T274I). The telSMN mutations identified to date cluster at the 3' end, in a region containing sites for SMN oligomerization and binding of Sm proteins. Interestingly, the novel A2G missense mutation occurs outside this conserved carboxy-terminal domain, closely upstream of an SIP1 (SMN-interacting protein 1) binding site. In three patients, the A2G mutation was found to be on the same allele as a rare polymorphism in the 5' UTR, providing evidence for a founder chromosome; Ag1-CA marker data also support evidence of an ancestral origin for the 800ins11 and 542delGT mutations. We note that telSMN missense mutations are associated with milder disease in our patients and that the severe type I SMA phenotype caused by frameshift mutations can be ameliorated by an increase in cenSMN gene copy number. PMID:9837824

  14. 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.

  15. Carrying our founders' mission overseas.

    PubMed

    Williams, Patricia A

    2006-01-01

    Catholic' health care providers have a calling to care for people in need, and that mission does not stop at geographical boundaries. In fact, U.S. health facilities in many cases were founded by overseas religious communities with a mission. Providing aid internationally enables U.S. sites to carry on that legacy. Although Americans traveling overseas to provide aid usually expect to be "teachers", they often find themselves becoming "students" instead. They learn to provide care without the advanced technology that is available in developed countries. They often experience cultures in which people can only hope for care access and in which patients are deeply appreciative of the services they receive. This type of education can change U.S. health care providers' perspective of their role and of the services they deliver. While gaining this wisdom-and imparting their own knowledge-providers also affect the quality of life of people in developing countries. In the end, global aid can create a better world for everyone, benefiting not only the recipients but also the worldwide community. When developing countries become more stable, develop stronger infrastructures, and have healthier citizens, other countries benefit from this progress.

  16. Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.

    PubMed

    Gerards, Mike; Kamps, Rick; van Oevelen, Jo; Boesten, Iris; Jongen, Eveline; de Koning, Bart; Scholte, Hans R; de Angst, Isabel; Schoonderwoerd, Kees; Sefiani, Abdelaziz; Ratbi, Ilham; Coppieters, Wouter; Karim, Latifa; de Coo, René; van den Bosch, Bianca; Smeets, Hubert

    2013-03-01

    , Moroccan patients with Leigh syndrome should be tested for the c.20C>A founder mutation in SLC19A3.

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

    PubMed

    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

    2015-08-01

    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.

  18. 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; ...

    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

  19. 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.

  20. 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

  1. Small-scale lithospheric foundering beneath the Peruvian Altiplano: evidence from back arc potassic volcanic rocks and lower crustal and mantle xenoliths

    NASA Astrophysics Data System (ADS)

    Chapman, A. D.; Ducea, M. N.

    2013-12-01

    asthenospheric mantle beneath the back arc provides one scenario satisfying these observations. However, geophysical evidence for the persistence of a dense keel of lower crust beneath the Peruvian Altiplano argues strongly against wholesale removal of a large body of lithospheric material. Furthermore, high-K magmatism in the back arc is volumetrically minor, contrary to the copious amounts of depleted magma expected from upwelling asthenosphere during a large-scale delamination event. We suggest that suite 1 back arc potassic mafic magmas resulted from dehydration partial melting in a small (< ~50 km) downgoing drip. The apparent spatial restriction of the hypothetical delaminating domain to a zone of active transtension (the Cusco-Vilcanota fault system) may reflect an increase in gravitational potential energy associated with drip detachment. The integrated effects of multiple small scale foundering events may provide a mechanism for isostatic uplift of orogenic plateaux, such as the Altiplano.

  2. Molecular Analysis of Hereditary Nonpolyposis Colorectal Cancer in the United States: High Mutation Detection Rate among Clinically Selected Families and Characterization of an American Founder Genomic Deletion of the MSH2 Gene

    PubMed Central

    Wagner, Anja; Barrows, Alicia; Wijnen, Juul Th.; van der Klift, Heleen; Franken, Patrick F.; Verkuijlen, Paul; Nakagawa, Hidewaki; Geugien, Marjan; Jaghmohan-Changur, Shantie; Breukel, Cor; Meijers-Heijboer, Hanne; Morreau, Hans; van Puijenbroek, Marjo; Burn, John; Coronel, Stephany; Kinarski, Yulia; Okimoto, Ross; Watson, Patrice; Lynch, Jane F.; de la Chapelle, Albert; Lynch, Henry T.; Fodde, Riccardo

    2003-01-01

    The identification of germline mutations in families with HNPCC is hampered by genetic heterogeneity and clinical variability. In previous studies, MSH2 and MLH1 mutations were found in approximately two-thirds of the Amsterdam-criteria–positive families and in much lower percentages of the Amsterdam-criteria–negative families. Therefore, a considerable proportion of HNPCC seems not to be accounted for by the major mismatch repair (MMR) genes. Does the latter result from a lack of sensitivity of mutation detection techniques, or do additional genes underlie the remaining cases? In this study we address these questions by thoroughly investigating a cohort of clinically selected North American families with HNPCC. We analyzed 59 clinically well-defined U.S. families with HNPCC for MSH2, MLH1, and MSH6 mutations. To maximize mutation detection, different techniques were employed, including denaturing gradient gel electrophoresis, Southern analysis, microsatellite instability, immunohistochemistry, and monoallelic expression analysis. In 45 (92%) of the 49 Amsterdam-criteria–positive families and in 7 (70%) of the 10 Amsterdam-criteria–negative families, a mutation was detected in one of the three analyzed MMR genes. Forty-nine mutations were in MSH2 or MLH1, and only three were in MSH6. A considerable proportion (27%) of the mutations were genomic rearrangements (12 in MSH2 and 2 in MLH1). Notably, a deletion encompassing exons 1–6 of MSH2 was detected in seven apparently unrelated families (12% of the total cohort) and was subsequently proven to be a founder. Screening of a second U.S. cohort with HNPCC from Ohio allowed the identification of two additional kindreds with the identical founder deletion. In the present study, we show that optimal mutation detection in HNPCC is achieved by combining accurate and expert clinical selection with an extensive mutation detection strategy. Notably, we identified a common North American deletion in MSH2, accounting

  3. 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

  4. 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.

  5. 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

    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

    2015-09-28

    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.

  6. The A1555G mutation in the 12S rRNA gene of human mtDNA: recurrent origins and founder events in families affected by sensorineural deafness.

    PubMed

    Torroni, A; Cruciani, F; Rengo, C; Sellitto, D; López-Bigas, N; Rabionet, R; Govea, N; López De Munain, A; Sarduy, M; Romero, L; Villamar, M; del Castillo, I; Moreno, F; Estivill, X; Scozzari, R

    1999-11-01

    The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to >/=30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from presymptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments.

  7. The A1555G Mutation in the 12S rRNA Gene of Human mtDNA: Recurrent Origins and Founder Events in Families Affected by Sensorineural Deafness

    PubMed Central

    Torroni, Antonio; Cruciani, Fulvio; Rengo, Chiara; Sellitto, Daniele; López-Bigas, Núria; Rabionet, Raquel; Govea, Nancy; López de Munain, Adolfo; Sarduy, Maritza; Romero, Lourdes; Villamar, Manuela; del Castillo, Ignacio; Moreno, Felipe; Estivill, Xavier; Scozzari, Rosaria

    1999-01-01

    Summary The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to ⩾30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from presymptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments. PMID:10521300

  8. 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.

  9. 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

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

    PubMed

    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.

  11. 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.

  12. 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.

  13. 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 .

  14. [Claude Bernard, founder of experimental physiology].

    PubMed

    Ren, Y; Li, X; Xu, W

    2001-07-01

    Claude Bernard was a famous French physiologist and philosopher in the 19th century. His experimental researches almost involved all fields of physiology. It is generally recognized by physiologists that in the research of Bernard in the digestion of pancreas, glucogenesis in the liver, and the vasomotor mechanism and the mechanism of action of curari and carbon monoxide were all at the lead. His researches established the foundation for modern physiology, modern biochemistry and the works of Pavlov, and were the initiation of experimental physiology.

  15. Questioning the Founders--and Ourselves

    ERIC Educational Resources Information Center

    Lindsay, Thomas K.

    2012-01-01

    The question of the relation between liberal education and political liberty, perennially important, is driven for this forum by the Obama administration's endorsement of "A Crucible Moment: College Learning & Democracy's Future," according to which the chief ends of postsecondary civic education ought to include the promotion of sweeping…

  16. 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...

  17. [Physician founders of pediatric pulmonology in Serbia].

    PubMed

    Pesić, Vladimir; Pavlović, Budimir

    2003-01-01

    Initial steps in the field of pediatric pulmology in Serbia were made by the first Serbian pediatricians Dr. Platon Papakostopulo (1864-1915) and Dr. Milenko Materni (1875-1929). Later on these steps were continued by Prim Dr. Ljubomir Vulović (1896-1970). Until the discovery of anti-tuberculotics, lung tuberculosis was one of the most frequent and most serious diseases among the adults and the children's population. Prof. Dr. Smilja Kostić-Joksić (1895-1981) and Prof. Dr Borivoje Tasovac (1907-1996) played a prominent role in the application and efficiency evaluation of BCG vaccines amount the Children in Sebia, along with the other chest disease studies. Immediately after the Second World War, Special Children's Hospital for Tuberculosis was set up, in 1945 in Belgrade. The Hospital had been successfully managed for a long period of time by Prim. Bojana Roknić (1900-1976). From 1960 to 1970 the Hospital was transformed in Special Children's Hospital for Chese Disense and Tuberculosis and was the only hospital in Serbia dealing with diagonistics, therapy and rehabilitation of children's chest diseases, before all asthma, recidive bronchitis and other chronical and recidive bronchopulmonal diseases. From 1970 until now on the postgraduate course in Pulmonology on the Faculty of Medicine, University of Belgrade, graduated over a hundred pediatricians.

  18. Diversification in the HIV-1 Envelope Hyper-variable Domains V2, V4, and V5 and Higher Probability of Transmitted/Founder Envelope Glycosylation Favor the Development of Heterologous Neutralization Breadth.

    PubMed

    Smith, S Abigail; Burton, Samantha L; Kilembe, William; Lakhi, Shabir; Karita, Etienne; Price, Matt; Allen, Susan; Hunter, Eric; Derdeyn, Cynthia A

    2016-11-01

    A recent study of plasma neutralization breadth in HIV-1 infected individuals at nine International AIDS Vaccine Initiative (IAVI) sites reported that viral load, HLA-A*03 genotype, and subtype C infection were strongly associated with the development of neutralization breadth. Here, we refine the findings of that study by analyzing the impact of the transmitted/founder (T/F) envelope (Env), early Env diversification, and autologous neutralization on the development of plasma neutralization breadth in 21 participants identified during recent infection at two of those sites: Kigali, Rwanda (n = 9) and Lusaka, Zambia (n = 12). Single-genome analysis of full-length T/F Env sequences revealed that all 21 individuals were infected with a highly homogeneous population of viral variants, which were categorized as subtype C (n = 12), A1 (n = 7), or recombinant AC (n = 2). An extensive amino acid sequence-based analysis of variable loop lengths and glycosylation patterns in the T/F Envs revealed that a lower ratio of NXS to NXT-encoded glycan motifs correlated with neutralization breadth. Further analysis comparing amino acid sequence changes, insertions/deletions, and glycan motif alterations between the T/F Env and autologous early Env variants revealed that extensive diversification focused in the V2, V4, and V5 regions of gp120, accompanied by contemporaneous viral escape, significantly favored the development of breadth. These results suggest that more efficient glycosylation of subtype A and C T/F Envs through fewer NXS-encoded glycan sites is more likely to elicit antibodies that can transition from autologous to heterologous neutralizing activity following exposure to gp120 diversification. This initiates an Env-antibody co-evolution cycle that increases neutralization breadth, and is further augmented over time by additional viral and host factors. These findings suggest that understanding how variation in the efficiency of site-specific glycosylation influences

  19. Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost

    PubMed Central

    Hulot, Sandrine L.; Korber, Bette; Giorgi, Elena E.; Vandergrift, Nathan; Saunders, Kevin O.; Balachandran, Harikrishnan; Mach, Linh V.; Lifton, Michelle A.; Pantaleo, Giuseppe; Tartaglia, Jim; Phogat, Sanjay; Jacobs, Bertram; Kibler, Karen; Perdiguero, Beatriz; Gomez, Carmen E.; Esteban, Mariano; Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.; Parks, Robert; Lloyd, Krissey; Sutherland, Laura; Scearce, Richard; Letvin, Norman L.; Seaman, Michael S.; Alam, S. Munir; Montefiori, David; Liao, Hua-Xin; Haynes, Barton F.

    2015-01-01

    ABSTRACT An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4+ and CD8+ T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using in silico-designed centralized immunogens for global HIV-1 vaccine development strategies. IMPORTANCE There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1

  20. 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

  1. Diversification in the HIV-1 Envelope Hyper-variable Domains V2, V4, and V5 and Higher Probability of Transmitted/Founder Envelope Glycosylation Favor the Development of Heterologous Neutralization Breadth

    PubMed Central

    Smith, S. Abigail; Burton, Samantha L.; Kilembe, William; Lakhi, Shabir; Karita, Etienne; Allen, Susan; Hunter, Eric; Derdeyn, Cynthia A.

    2016-01-01

    A recent study of plasma neutralization breadth in HIV-1 infected individuals at nine International AIDS Vaccine Initiative (IAVI) sites reported that viral load, HLA-A*03 genotype, and subtype C infection were strongly associated with the development of neutralization breadth. Here, we refine the findings of that study by analyzing the impact of the transmitted/founder (T/F) envelope (Env), early Env diversification, and autologous neutralization on the development of plasma neutralization breadth in 21 participants identified during recent infection at two of those sites: Kigali, Rwanda (n = 9) and Lusaka, Zambia (n = 12). Single-genome analysis of full-length T/F Env sequences revealed that all 21 individuals were infected with a highly homogeneous population of viral variants, which were categorized as subtype C (n = 12), A1 (n = 7), or recombinant AC (n = 2). An extensive amino acid sequence-based analysis of variable loop lengths and glycosylation patterns in the T/F Envs revealed that a lower ratio of NXS to NXT-encoded glycan motifs correlated with neutralization breadth. Further analysis comparing amino acid sequence changes, insertions/deletions, and glycan motif alterations between the T/F Env and autologous early Env variants revealed that extensive diversification focused in the V2, V4, and V5 regions of gp120, accompanied by contemporaneous viral escape, significantly favored the development of breadth. These results suggest that more efficient glycosylation of subtype A and C T/F Envs through fewer NXS-encoded glycan sites is more likely to elicit antibodies that can transition from autologous to heterologous neutralizing activity following exposure to gp120 diversification. This initiates an Env-antibody co-evolution cycle that increases neutralization breadth, and is further augmented over time by additional viral and host factors. These findings suggest that understanding how variation in the efficiency of site-specific glycosylation influences

  2. 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.

  3. [Dentist William Morton is a founder of general anesthesia].

    PubMed

    Pavlovskiĭ, L N

    2005-01-01

    The article presents history of discovery of general anesthesia. Scientists had come up with an idea of using and effects of anesthesia as long ago as almost 50 years before it was used in the practice. American dentist William Morton alone for the first time succeeded in right using effects of general anesthesia in practice.

  4. 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.

  5. 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.

  6. [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.

  7. 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.

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

    NASA Astrophysics Data System (ADS)

    Dullo, Wolf-Christian; Pfaffl, Fritz A.

    2016-11-01

    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.

  9. 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.

  10. [Johann Friedrich Meckel, Jr. as founder of scientific teratology].

    PubMed

    Schierhorn, H

    1984-01-01

    n the occasion of the 150th anniversary of his death, the scientific work of the famous German anatomist Johann Friedrich Meckel (1781 to 1833) in Halle is appreciated. The Younger Meckel is counted to the most outstanding figures in the history of anatomy and medicine in the first third of 19th century. According to his founded knowledges in the normal, comparative, and pathologic anatomy and embryology he was able to give a scientific argument of malformations first of all in the history of medicine and biology. The edition of Meckel's Handbook of Pathologic Anatomy (in German language; 1st vol. 1812) is the birth of scientific teratology. Through his contributions to teratology Meckel directly participated in the raising of general pathology and pathologic anatomy to scientific disciplines. Meckel's interceding for C. F. Wolff's theory of epigenesis, not at last by translation of Wolff's paper "De formatione intestinorum" (1768 to 1769) into the German language, accelerated the development of the general and special embryology during the 19th century. In the contemporary medicine the succeeding eponyms are reminding of the imposing German physician and anatomist: the Meckel's diverticulum of ileum (1809), the Meckel's cartilage of the mandibular arch (1820) and the so-called Meckel syndrome (1822).

  11. [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.

  12. 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

  13. Migration of founder epithelial cells drives proper molar tooth positioning and morphogenesis

    PubMed Central

    Prochazka, Jan; Prochazkova, Michaela; Du, Wen; Spoutil, Frantisek; Tureckova, Jolana; Hoch, Renee; Shimogori, Tomomi; Sedlacek, Radislav; Rubenstein, John L.; Wittmann, Torsten; Klein, Ophir D.

    2015-01-01

    Summary 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. PMID:26702830

  14. [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.

  15. 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…

  16. Comment on "Phonemic diversity supports a serial founder effect model of language expansion from Africa".

    PubMed

    Cysouw, Michael; Dediu, Dan; Moran, Steven

    2012-02-10

    We show that Atkinson's (Reports, 15 April 2011, p. 346) intriguing proposal--that global linguistic diversity supports a single language origin in Africa--is an artifact of using suboptimal data, biased methodology, and unjustified assumptions. We criticize his approach using more suitable data, and we additionally provide new results suggesting a more complex scenario for the emergence of global linguistic diversity.

  17. 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:

  18. 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.

  19. 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.

  20. High genetic diversity and absence of founder effects in a worldwide aquatic invader.

    PubMed

    Lejeusne, Christophe; Saunier, Alice; Petit, Nicolas; Béguer, Mélanie; Otani, Michio; Carlton, James T; Rico, Ciro; Green, Andy J

    2014-07-24

    The introduced oriental shrimp Palaemon macrodactylus has recently become widespread in temperate estuaries worldwide. However, this recent worldwide spread outside of its native range arises after a previous introduction to the US Pacific coast, where it was restricted for more than 30 years. Using a phylogeographic approach, the present work investigates the genetic history of the invasion of this decapod worldwide. Japan acted as the main native source area for worldwide introduced populations, but other native areas (likely South Korea and China) may act as source populations as well. The recently introduced European and NW Atlantic populations result from colonization from both Japan and an unknown area of the native range, although colonization from the NE Pacific could not be ruled out. Most introduced populations had higher haplotypic diversity than most native populations. P. macrodactylus has a strong potential to become one of the most widespread introduced species and may become the dominant estuarine shrimp in Europe. The ecological and economic consequences of this invasion remain to be thoroughly evaluated.

  1. On the Retirement of E.P. Goldfinch, Founder of Radiation Protection Dosimetry

    SciTech Connect

    McDonald, Joseph C.; Horowitz, Yigal S.

    2004-08-01

    This special issue of Radiation Protection Dosimetry commemorates the many years of service Eddie has dedicated to the international radiation protection community. Beginning with its first issue in 1981, Eddie led RPD to its current prominence with a guiding hand and Solomon-like wisdom, coupled with keen common sense which will be sorely missed. But, there is no doubt that the journal he created will continue to flourish in the foreseeable future.

  2. The Matrilineal Ancestry of Ashkenazi Jewry: Portrait of a Recent Founder Event

    PubMed Central

    Behar, Doron M.; Metspalu, Ene; Kivisild, Toomas; Achilli, Alessandro; Hadid, Yarin; Tzur, Shay; Pereira, Luisa; Amorim, Antonio; Quintana-Murci, Lluís; Majamaa, Kari; Herrnstadt, Corinna; Howell, Neil; Balanovsky, Oleg; Kutuev, Ildus; Pshenichnov, Andrey; Gurwitz, David; Bonne-Tamir, Batsheva; Torroni, Antonio; Villems, Richard; Skorecki, Karl

    2006-01-01

    Both the extent and location of the maternal ancestral deme from which the Ashkenazi Jewry arose remain obscure. Here, using complete sequences of the maternally inherited mitochondrial DNA (mtDNA), we show that close to one-half of Ashkenazi Jews, estimated at 8,000,000 people, can be traced back to only 4 women carrying distinct mtDNAs that are virtually absent in other populations, with the important exception of low frequencies among non-Ashkenazi Jews. We conclude that four founding mtDNAs, likely of Near Eastern ancestry, underwent major expansion(s) in Europe within the past millennium. PMID:16404693

  3. [ZHU Lian--the founder of Chinese acupuncture-moxibustion scientific research].

    PubMed

    Su, Yang-Shuai; Liu, Bing; Jing, Xiang-Hong; He, Wei; Wang, Xiao-Yu; Zhang, Li-Jian

    2014-12-01

    This article discussed ZHU Lian's contributions to acupuncture-moxibustion scientific research from three aspects: building the scientific thought of "new acupuncture-moxibustion", constructing the first domestic acupuncture-moxibustion institution and opening the door to modern acupuncture-moxibustion scientific research. ZHU Lian's visionary thought of "new acupuncture-moxibustion" has influenced the following researchers till now. She established the acupuncture-Moxibustion therapeutic institute affiliated to the Ministry of Health, set up the acupuncture-Moxibustion research platforms and teams and made research cooperation. She firstly carried out acupuncture-Moxibustion clinical and basic scientific research, which started the acupuncture-Moxi- bustion scientific research in China. ZHU Lian is the Pioneer of Chinese acupuncture-Moxibustion scientific research.

  4. Evidence of long-lived founder virus in mother-to-child HIV transmission.

    PubMed

    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.

  5. Isaac Judaeus Israeli: a Jewish founder of the origins of nephrology.

    PubMed

    Massry, Shaul G

    2009-01-01

    This paper discusses the Book of Urine in the Opera Omnia Isaci of Isaac Judaeus Israeli. Born in Egypt in the middle of the ninth century, Isaac Judaeus was considered a genius by his peers. The book accepted Galen's ideas and expanded them. Its original contribution was in the concept of the seeping of fluid and sediment from blood into the kidney and from the kidney to the bladder. This concept corresponds to glomerular filtration and tubular secretion.

  6. Aleksandr Pavlovich Gulyaev: founder of a school of classical metals science

    NASA Astrophysics Data System (ADS)

    Volynova, T. F.

    2008-11-01

    The works of A. P. Gulyaev performed at MAI, TsNIITMASh, and TsNIIchermet and devoted to various aspects of theoretical and applied metals science are analyzed. Professor T. F. Volynova, a disciple of Gulyaev, a Doctor of Engineering, an active member of the New York Academy of Sciences since 1995, heads the Laboratory for Problems of Metals Science created by Gulyaev. In the encyclopedic edition of "WHO IS WHO IN RUSSIAN METALLURGY" of 1999 she is included in the list of leading Russian specialists in the field. Her interests cover creation of new classes of multifunctional materials, high-strength nonmagnetic, damping, and antifriction alloys, and wear-resistant tool and structural materials for general and special engineering.

  7. A founder TMIE mutation is a frequent cause of hearing loss in southeastern Anatolia.

    PubMed

    Sirmaci, A; Oztürkmen-Akay, H; Erbek, S; Incesulu, A; Duman, D; Taşir-Yilmaz, S; Ozdağ, H; Tekin, M

    2009-06-01

    Using Affymetrix 10K arrays, we searched for regions of homozygosity in 51 Turkish families including at least three members with either congenital or prelingual autosomal recessive non-syndromic sensorineural hearing loss (ARNSSNHL), and identified four families whose deafness mapped to the DFNB6 locus on 3p21 containing the TMIE gene. Mutation analysis revealed the p.R84W mutation in all four families. Screening of this mutation in 254 families with ARNSSNHL, without GJB2 mutations, revealed four additional affected families. A novel mutation was found in a non-complementary marriage between a deaf couple who were homozygous for p.R84W and p.W57X, respectively with two affected children who were compound heterozygotes. Six of the TMIE families originated from southeastern Anatolia, making p.R84W a common cause of hearing loss in that region with a relative frequency of 10.3% (95% CI is 2.5-18.1%). The overall prevalence of the p.R84W mutation in ARNSSNHL in Turkey is 2.4% (95% CI is 0.7-4.0%). Genotyping of single-nucleotide polymorphisms flanking the TMIE gene revealed a conserved haplotype, suggesting a single origin for p.R84W from a common ancestor 1250 years ago (95% CI is 650-2500 years). We conclude that p.R84W could be a common mutation in other Middle Eastern populations and should be included in mutation screening offered to individuals with ARNSSNHL.

  8. 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.

  9. [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.

  10. Laura Carnell: The Woman behind the Founder's Myth at Temple University

    ERIC Educational Resources Information Center

    Bakley, Annette McMenamin

    2014-01-01

    Using archival materials from the early years of Temple University's history at the Special Collections Research Center, Templana Collection, at Samuel Paley Library of Temple University as well as historical periodicals, this project established a biographical sketch of Associate President Laura Carnell and examined her influence on the…

  11. 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)

  12. High genetic diversity and absence of founder effects in a worldwide aquatic invader

    PubMed Central

    Lejeusne, Christophe; Saunier, Alice; Petit, Nicolas; Béguer, Mélanie; Otani, Michio; Carlton, James T.; Rico, Ciro; Green, Andy J.

    2014-01-01

    The introduced oriental shrimp Palaemon macrodactylus has recently become widespread in temperate estuaries worldwide. However, this recent worldwide spread outside of its native range arises after a previous introduction to the US Pacific coast, where it was restricted for more than 30 years. Using a phylogeographic approach, the present work investigates the genetic history of the invasion of this decapod worldwide. Japan acted as the main native source area for worldwide introduced populations, but other native areas (likely South Korea and China) may act as source populations as well. The recently introduced European and NW Atlantic populations result from colonization from both Japan and an unknown area of the native range, although colonization from the NE Pacific could not be ruled out. Most introduced populations had higher haplotypic diversity than most native populations. P. macrodactylus has a strong potential to become one of the most widespread introduced species and may become the dominant estuarine shrimp in Europe. The ecological and economic consequences of this invasion remain to be thoroughly evaluated. PMID:25060780

  13. 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.

  14. 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

  15. A founder mutation causing a severe methylenetetrahydrofolate reductase (MTHFR) deficiency in Bukharian Jews.

    PubMed

    Ben-Shachar, Shay; Zvi, Tal; Rolfs, Arndt; Breda Klobus, Andrea; Yaron, Yuval; Bar-Shira, Anat; Orr-Urtreger, Avi

    2012-11-01

    Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. A novel homozygous MTHFR c.474A>T (p.G158G) mutation was detected in two unrelated children of Jewish Bukharian origin. This mutation generates an abnormal splicing and early termination codon. A carrier frequency of 1:39 (5/196) was determined among unrelated healthy Bukharian Jews. Given the disease severity and allele frequency, a population screening for individuals of this ancestry is warranted in order to allow prenatal, or preimplantation diagnosis.

  16. 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.

  17. Society for Reproductive Biology Founders' Lecture 2006 - life in the pouch: womb with a view.

    PubMed

    Renfree, Marilyn B

    2006-01-01

    Marsupials give birth to an undeveloped altricial young after a relatively short gestation period, but have a long and sophisticated lactation with the young usually developing in a pouch. Their viviparous mode of reproduction trades placentation for lactation, exchanging the umbilical cord for the teat. The special adaptations that marsupials have developed provide us with unique insights into the evolution of all mammalian reproduction. Marsupials hold many mammalian reproductive 'records', for example they have the shortest known gestation but the longest embryonic diapause, the smallest neonate but the longest sperm. They have contributed to our knowledge of many mammalian reproductive events including embryonic diapause and development, birth behaviour, sex determination, sexual differentiation, lactation and seasonal breeding. Because marsupials have been genetically isolated from eutherian mammals for over 125 million years, sequencing of the genome of two marsupial species has made comparative genomic biology an exciting and important new area of investigation. This review will show how the study of marsupials has widened our understanding of mammalian reproduction and development, highlighting some mechanisms that are so fundamental that they are shared by all today's marsupial and eutherian mammals.

  18. Why William James Might Be Considered the Founder of the Scientist-Practitioner Model.

    ERIC Educational Resources Information Center

    Howard, George S.

    1993-01-01

    Argues that close examination of William James's more philosophically oriented works reveals a set of principles (i.e., pragmatism, pluralism, radical empiricism, strenuosity, and freedom of the will) that form the basis of the scientist-practitioner model in psychology. (Author/NB)

  19. Founders of a profession: the original subscribers to the first dental journal in the world.

    PubMed

    Ring, Malvin E

    2005-01-01

    A true profession is built upon a tripod: a formal organization, formal professional education, and a formal scientific literature. The United States was the leader in all three. In 1839-40, the American Society of Dental Surgeons was organized, the Baltimore College of Dental Surgery was established, and the first dental journal in the world, the American Journal of Dental Science, was founded. At that time there were only about three hundred trained and scientific dentists in the entire country; the rest were relatively untrained operators, outright quacks, or charlatans. In 1898, a list of the first subscribers to the first journal was discovered and published by G.V. Black. These initial subscribers may be considered the core group of truly professional American dentists. They became the leaders of the newly born profession of dentistry. Short biographies of some of them are included.

  20. 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

  1. 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.

  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. Myotonia and the muscle chloride channel: dominant mutations show variable penetrance and founder effect.

    PubMed

    Koty, P P; Pegoraro, E; Hobson, G; Marks, H G; Turel, A; Flagler, D; Cadaldini, M; Angelini, C; Hoffman, E P

    1996-10-01

    The delayed relaxation or sustained contraction of skeletal muscle-myotonia-is frequently seen in myotonic dystrophy and sodium channelopathies (hyperkalemic periodic paralysis, paramyotonia congenita). Many cases of congenital myotonia without other clinical symptoms have been associated with mutations in the muscle chloride channel gene. Most cases reported to date show a recessive inheritance pattern, with loss of function of the corresponding protein. Six families have been reported with dominantly inherited myotonia and mutations of the chloride channel gene. Here we report clinical and molecular data on 38 family members from four new families with dominantly inherited myotonia congenita. Three families show a previously characterized G230E mutation, and we show that these three share a common affected ancestor despite living in different regions of the United States (linkage disequilibrium). One Italian family is shown to have a novel dominant mutation-I290M. This is the sixth mutation identified in Thomsen's myotonia. Genotype/phenotype correlations in these four families showed that both of the dominant mutations resulted in a mild clinical picture in 90% of the patients, and no symptoms in 10% of mutation-positive patients. The EMG was the clinical feature that most closely correlated with mutation data; however, 3 of 16 (19%) mutation-positive patients tested negative by electromyography at least once, and 1 (6%) tested negative despite multiple tests. Only about half (55%) of the mutation-positive patients tested positive for percussion myotonia. Most of the clinically symptomatic individuals stated that cold temperatures and stress substantially worsened their myotonia. Our data show that dominantly inherited Thomsen's myotonia is most often a very mild disorder that shows considerable clinical heterogeneity.

  4. 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.

  5. 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...

  6. 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)

  7. To Live Fulfilled: George Peabody, 1795-1869, Founder of George Peabody College for Teachers.

    ERIC Educational Resources Information Center

    Parker, Franklin

    1994-01-01

    One in a collection of papers on self-made millionaire and educational philanthropist George Peabody highlights his establishment of the Peabody Education Fund, noting the far-reaching effects of that gift to southern education. The paper also presents a brief history of the life, work, and death of George Peabody. (SM)

  8. 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),…

  9. 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.

  10. 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...

  11. [V. V. Strel'tsov: founder of the Institute and father of our country's aerospace medicine].

    PubMed

    Agadzhanian, N A

    1996-01-01

    The paper gives an account of the scientific-and-practical activity of the prominent Soviet physiologist V. V. Streltsov, Head of the Fourth Sector, Research Sanitary Institute, and the initiator of the Aviation Medicine Institute. He was a brilliant experimenter, innovator, organizer of unique researches who developed the physiological aspects of high altitude, speedy, night and instrumental blind flights, the problems of stratospheric aviation. He made the first experimental ascent in the altitude chamber. He was one of the first aviation physicians who made a parachute jump. He was the first inflight medical investigator who tested the on-board oxygen equipment in group cross-country flight on the closed route Moscow-Kharkov-Moscow.

  12. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

    PubMed

    Sabatti, Chiara; Service, Susan K; Hartikainen, Anna-Liisa; Pouta, Anneli; Ripatti, Samuli; Brodsky, Jae; Jones, Chris G; Zaitlen, Noah A; Varilo, Teppo; Kaakinen, Marika; Sovio, Ulla; Ruokonen, Aimo; Laitinen, Jaana; Jakkula, Eveliina; Coin, Lachlan; Hoggart, Clive; Collins, Andrew; Turunen, Hannu; Gabriel, Stacey; Elliot, Paul; McCarthy, Mark I; Daly, Mark J; Järvelin, Marjo-Riitta; Freimer, Nelson B; Peltonen, Leena

    2009-01-01

    Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

  13. Targeted carrier screening for four recessive disorders: high detection rate within a founder population.

    PubMed

    Mathijssen, Inge B; Henneman, Lidewij; van Eeten-Nijman, Janneke M C; Lakeman, Phillis; Ottenheim, Cecile P E; Redeker, Egbert J W; Ottenhof, Winnie; Meijers-Heijboer, Hanne; van Maarle, Merel C

    2015-03-01

    In a genetically isolated community in the Netherlands four severe recessive genetic disorders occur at relatively high frequency (pontocerebellar hypoplasia type 2 (PCH2), fetal akinesia deformation sequence (FADS), rhizomelic chondrodysplasia punctata type 1 (RCDP1), and osteogenesis imperfecta (OI) type IIB/III. Over the past decades multiple patients with these disorders have been identified. This warranted the start of a preconception outpatient clinic, in 2012, aimed at couples planning a pregnancy. The aim of our study was to evaluate the offer of targeted genetic carrier screening as a method to identify high-risk couples for having affected offspring in this high-risk subpopulation. In one year, 203 individuals (92 couples and 19 individuals) were counseled. In total, 65 of 196 (33.2%) tested individuals were carriers of at least one disease, five (7.7%) of them being carriers of two diseases. Carrier frequencies of PCH2, FADS, RCDP1, and OI were 14.3%, 11.2%, 6.1%, and 4.1% respectively. In individuals with a positive family history for one of the diseases, the carrier frequency was 57.8%; for those with a negative family history this was 25.8%. Four PCH2 carrier-couples were identified. Thus, targeted (preconception) carrier screening in this genetically isolated population in which a high prevalence of specific disorders occurs detects a high number of carriers, and is likely to be more effective compared to cascade genetic testing. Our findings and set-up can be seen as a model for carrier screening in other high-risk subpopulations and contributes to the discussion about the way carrier screening can be offered and organized in the general population.

  14. 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.

  15. 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.

  16. On Yesterday: Paul Levinson, President and Founder of Connected Education, Inc.

    ERIC Educational Resources Information Center

    TECHNOS, 1999

    1999-01-01

    This interview with author Paul Levinson applies Marshall McLuhans' ideas regarding media to today's society, the Internet and the Web, and their effects on human communication and education. Highlights include societal change; teachers as gatekeepers; accreditation of online college courses; the global village; and control of technology. (LRW)

  17. The Founders' and Benefactors' Lecture. General dental practice--the evolution of a discipline.

    PubMed

    Lowndes, P

    1997-10-25

    My subject is the development of general dental practice from its roots in antiquity; through the Victorian concerns to protect the public by formalising registration and training; past the present day with our enthusiasms for postgraduate education and on into the future. In the course of this journey, I will seek to demonstrate that general practice is changing from the provider of basic solutions to basic problems and becoming a complex, multi-layered career. Indeed, that it is becoming a discipline in its own right.

  18. Foundering and Exhumation of UHP Terranes: Race Car or School Bus?

    NASA Astrophysics Data System (ADS)

    Kylander-Clark, A. R.; Hacker, B. R.

    2008-12-01

    Recent geochronologic data from the giant ultrahigh-pressure (UHP) terrane, in the Western Gneiss Region of Norway, indicate that subduction and exhumation were relatively slow (a few mm/yr), and that the terrane was exhumed to the surface as a relatively thick, coherent body. These conclusions are in stark contrast to those reached in previous studies of some of the best-studied, smaller UHP terranes and suggest that the processes that form and/or exhume small UHP terranes are fundamentally different from the processes that affect large UHP terranes. These differences may be the result of variations in the buoyancy forces of different proportions of subducted felsic crust, mafic crust, and mantle lithosphere. Initial collision occurs via the subduction of smaller portions of continental material, such as microcontinents or ribbon continents. Because the proportion of continental crust is small, the processes involved in early UHP terrane formation are dominated by the oceanic slab; subduction rates are fast because average plate densities are high, and, as a result, subduction angles are steep. Because these smaller, thinner portions of crust are weak, they deform easily and mix readily with the mantle. As the collision matures, thicker and larger portions of continental material-such as a continental margin-are subducted, and the subduction regime changes from one that was ocean dominated to one that is continent dominated. The increased buoyancy of the larger volume of continental crust resists the pull of the leading oceanic lithosphere; subduction shallows and plate rates slow. Because the downgoing continent is thick, it is strong, remains cohesive and has limited interaction with the mantle. Although the subduction regime during early orogenesis is distinct from that during late orogenesis, the degree of mountain building and crustal thickening may be similar in both stages as small volumes and fast flow rates of buoyant material give way to large volumes and slow flow rates.

  19. Founders hope new venture-capital fund will spur medical, biotechnology research

    PubMed Central

    Gray, Charlotte

    1995-01-01

    Lack of a coherent industrial strategy and venture capital have hindered scientific researchers in Canada, but the Canadian Medical Discoveries Fund (CMDF) Inc. hopes to change that. Under the leadership of Dr. Henry Friesen, president of the Medical Research Council of Canada, and Dr. Calvin Stiller, head of the multiorgan transplant unit at University Hospital, London, Ont., the new fund proposes to invest in promising medical and biotechnology research companies in Canada. The research council's peerreview system gives the new fund scientific credibility.

  20. 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.

  1. 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.

  2. 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.

  3. High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia.

    PubMed

    Torres, Diana; Rashid, Muhammad Usman; Gil, Fabian; Umana, Angela; Ramelli, Giancarlo; Robledo, Jose Fernando; Tawil, Mauricio; Torregrosa, Lilian; Briceno, Ignacio; Hamann, Ute

    2007-06-01

    In South America, a high proportion of the population is of Hispanic origin with an important representation in Colombia. Since nothing is known about the contribution of BRCA1 and BRCA2 germline mutations to hereditary breast/ovarian cancer in the Hispanic population from Colombia, we conducted the first study of 53 breast/ovarian cancer families from this country. Comprehensive BRCA mutation screening was performed using a range of techniques, including DHPLC, SSCP, and PTT, followed by DNA sequencing analysis. Thirteen deleterious germline mutations (24.5%) were identified in 53 families, comprising eight in BRCA1 and five in BRCA2. The two recurrent BRCA1 mutations, 3450 delCAAG and A1708E, accounted for 100% of all BRCA1 mutations identified in this cohort and the recurrent 3034 delACAA BRCA2 mutation for 40% of all BRCA2 mutations. Haplotype analyses suggested that each of these mutations has arisen from a common ancestor. The prevalence of BRCA1 or BRCA2 mutations was 50% in multiple case breast cancer families, and was 33% for the breast-ovarian cancer families. Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Colombia. The spectrum of mutations differed completely to that previously reported in Hispanic families of predominantly Mexican origin from Southern California [1] suggesting that specific genetic risk assessment strategies for the different Hispanic populations in South America and in the United States need to be developed.

  4. Maple Syrup Urine Disease: Identification and Carrier-Frequency Determination of a Novel Founder Mutation in the Ashkenazi Jewish Population

    PubMed Central

    Edelmann, Lisa; Wasserstein, Melissa P.; Kornreich, Ruth; Sansaricq, Claude; Snyderman, Selma E.; Diaz, George A.

    2001-01-01

    Maple syrup urine disease (MSUD) is a rare, autosomal recessive disorder of branched-chain amino acid metabolism. We noted that a large proportion (10 of 34) of families with MSUD that were followed in our clinic were of Ashkenazi Jewish (AJ) descent, leading us to search for a common mutation within this group. On the basis of genotyping data suggestive of a conserved haplotype at tightly linked markers on chromosome 6q14, the BCKDHB gene encoding the E1β subunit was sequenced. Three novel mutations were identified in seven unrelated AJ patients with MSUD. The locations of the affected residues in the crystal structure of the E1β subunit suggested possible mechanisms for the deleterious effects of these mutations. Large-scale population screening of AJ individuals for R183P, the mutation present in six of seven patients, revealed that the carrier frequency of the mutant allele was ∼1/113; the patient not carrying R183P had a previously described homozygous mutation in the gene encoding the E2 subunit. These findings suggested that a limited number of mutations might underlie MSUD in the AJ population, potentially facilitating prenatal diagnosis and carrier detection of MSUD in this group. PMID:11509994

  5. 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 ...

  6. Molecular genetic and genetic correlations in sodium channelopathies: Lack of founder effect and evidence for a second gene

    SciTech Connect

    Wang, J.; Zhou, J.; Feero, W.G.; Conwit, R.; Galloway, G.; Hoffman, E.P. ); Wessel, H.B. Univ. of Pittsburgh, PA ); Todorovic, S.M. ); Barany, F. ); Hausmanowa-Petrusewicz, I.; Fidzianska, A. ); Arahata, K. ); Sillen, A. ); Marks, H.G. ); Hartlage, P. ); Ricker, K. ); Lehmann-Horn, F. ); Hayakawa, H. )

    1993-06-01

    The authors present a correlation of molecular genetic data (mutations) and genetic data (dinucleotide-repeat polymorphisms) for a cohort of seven hyperkalemic periodic paralysis (HyperPP) and two paramyotonia congenita (PC) families from diverse ethnic backgrounds. They found that each of three previously identified point mutations of the adult skeletal muscle sodium-channel gene occurred on two different dinucleotide-repeat haplotypes. These results indicate that dinucleotide-repeat haplotypes are not predictive of allelic heterogeneity in sodium channelopathies, contrary to previous suggestions. In addition, they identified a HyperPP pedigree in which the dominant disorder was not linked to the sodium-channel gene. Thus, a second locus can give rise to a similar clinical phenotype. Some individuals in this pedigree exhibited a base change causing the nonconservative substitution of an evolutionarily conserved amino acid. Because this change was not present in 240 normal chromosomes and was near another HyperPP mutation, it fulfilled the most commonly used criteria for being a mutation rather than a polymorphism. However, linkage studies using single-strand conformation polymorphism-derived and sequence-derived haplotypes excluded this base change as a causative mutation: these data serve as a cautionary example of potential pitfalls in the delineation of change-of-function point mutations. 35 refs., 5 figs., 1 tab.

  7. A Founder Mutation in PET100 Causes Isolated Complex IV Deficiency in Lebanese Individuals with Leigh Syndrome

    PubMed Central

    Lim, Sze Chern; Smith, Katherine R.; Stroud, David A.; Compton, Alison G.; Tucker, Elena J.; Dasvarma, Ayan; Gandolfo, Luke C.; Marum, Justine E.; McKenzie, Matthew; Peters, Heidi L.; Mowat, David; Procopis, Peter G.; Wilcken, Bridget; Christodoulou, John; Brown, Garry K.; Ryan, Michael T.; Bahlo, Melanie; Thorburn, David R.

    2014-01-01

    Leigh syndrome (LS) is a severe neurodegenerative disorder with characteristic bilateral lesions, typically in the brainstem and basal ganglia. It usually presents in infancy and is genetically heterogeneous, but most individuals with mitochondrial complex IV (or cytochrome c oxidase) deficiency have mutations in the biogenesis factor SURF1. We studied eight complex IV-deficient LS individuals from six families of Lebanese origin. They differed from individuals with SURF1 mutations in having seizures as a prominent feature. Complementation analysis suggested they had mutation(s) in the same gene but targeted massively parallel sequencing (MPS) of 1,034 genes encoding known mitochondrial proteins failed to identify a likely candidate. Linkage and haplotype analyses mapped the location of the gene to chromosome 19 and targeted MPS of the linkage region identified a homozygous c.3G>C (p.Met1?) mutation in C19orf79. Abolishing the initiation codon could potentially still allow initiation at a downstream methionine residue but we showed that this would not result in a functional protein. We confirmed that mutation of this gene was causative by lentiviral-mediated phenotypic correction. C19orf79 was recently renamed PET100 and predicted to encode a complex IV biogenesis factor. We showed that it is located in the mitochondrial inner membrane and forms a ∼300 kDa subcomplex with complex IV subunits. Previous proteomic analyses of mitochondria had overlooked PET100 because its small size was below the cutoff for annotating bona fide proteins. The mutation was estimated to have arisen at least 520 years ago, explaining how the families could have different religions and different geographic origins within Lebanon. PMID:24462369

  8. How Can Chapaati Be Transformed into Bread? Or How Innovation Can Founder on the Rock of Established Practices.

    ERIC Educational Resources Information Center

    Mangubhai, Francis

    Although the efficacy of educational innovation has basic implicit assumptions, this paper argues the need for contextual conditions such as curriculum, resources, teacher competence, and educational infrastructures as a point of departure for predicting the potential success of a proposed innovation. A discussion of the fundamental dynamics of…

  9. [Michael Fischer (1887-1948)--life and work of an important founder of Catholic nursing in Germany].

    PubMed

    Kolling, H

    2000-08-01

    In 1919, Michael Fischer OSC was appointed to the German charity union "Zentrale des Deutschen Caritasverbandes" (DCV) in Freiburg. He assumed his duties as the acting manager and general secretary for the German catholic union of health institutions "Verband Katholischer Kranken- und Pflegeanstalten". For nearly twenty years, he was involved in expanding and strengthening this specialized organisation. For more than a decade, Michael Fischer influenced catholic medical care in Germany by holding lectures; on the whole, he published the medical welfare journal "Krankendienst" as well as fifteen specialized books and more than five hundred articles in different journals, which were essential. For all his efforts, his enormous engagement, historical health research has ignored him until now. The following essay is meant to give insight into his life and works and pays tribute to his importance in nursing care.

  10. 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

  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. 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:…

  13. 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

  14. Parkinson's disease due to the R1441G mutation in Dardarin: a founder effect in the Basques.

    PubMed

    Simón-Sánchez, Javier; Martí-Massó, José-Félix; Sánchez-Mut, José Vicente; Paisán-Ruiz, Coro; Martínez-Gil, Angel; Ruiz-Martínez, Javier; Sáenz, Amets; Singleton, Andrew B; López de Munain, Adolfo; Pérez-Tur, Jordi

    2006-11-01

    The recent discovery of mutations in Dardarin (LRRK2) have been related to the appearance of Parkinson's disease in several families. Notably, one single mutation in this gene (R1441G) not only appeared in familial, but also in apparently sporadic Parkinson disease (PD) patients of Basque descent. A clinical population was ascertained, and subjects were classified into Basque and non-Basque descent according to their known ancestry. The R1441G mutation was assayed using an allele-specific polymerase chain reaction, and several single nucleotide polymorphisms surrounding this mutation were analyzed by direct sequencing. In addition to 22 members of the original Basque families where R1441G was identified, we observed 17 carriers of the mutation who were apparently related through a common ancestor. From a clinical perspective, the disease observed in mutation carriers is indistinguishable from that in noncarriers. The R1441G mutation causes a form of Parkinson's disease that is equivalent to that observed in idiopathic Parkinson's disease. This mutation appears in 16.4% and 4.0% of familial and sporadic PD in this Basque population, respectively.

  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. 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.

  17. Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.

    PubMed Central

    Friedman, L S; Szabo, C I; Ostermeyer, E A; Dowd, P; Butler, L; Park, T; Lee, M K; Goode, E L; Rowell, S E; King, M C

    1995-01-01

    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 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'-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. Images Figure 5 PMID:8533757

  18. [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.

  19. A resolution commemorating Dr. Norman Borlaug, recipient of the Nobel Peace Prize, Congressional Gold Medal, Presidential Medal of Freedom, and founder of the World Food Prize.

    THOMAS, 111th Congress

    Sen. Harkin, Tom [D-IA

    2009-09-16

    09/16/2009 Read twice and referred to the Committee on the Judiciary. (text of measure as introduced: CR S9441) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  20. A resolution commemorating Dr. Norman Borlaug, recipient of the Nobel Peace Prize, Congressional Gold Medal, Presidential Medal of Freedom, and founder of the World Food Prize.

    THOMAS, 111th Congress

    Sen. Harkin, Tom [D-IA

    2009-09-17

    09/17/2009 Submitted in the Senate, considered, and agreed to without amendment and with a preamble by Unanimous Consent. (consideration: CR S9571; text as passed Senate: CR S9571; text of measure as introduced: CR S9567-9568) (All Actions) Tracker: This bill has the status Passed SenateHere are the steps for Status of Legislation:

  1. 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.

  2. [Efim Ivanovich Smirnov--an outstanding founder of the military medicine and civil health care (to the 110th anniversary of birth)].

    PubMed

    Maksimov, I B; Krylov, N L

    2014-10-01

    In October 2014 we celebrate the 110th anniversary of the birth of Chief of the Main Military Medical Administration of the People's Commissariat of Defense, Minister of Health of the USSR, Hero of Socialist Labor, Member of the Academy of Medical Sciences of the USSR, Colonel-General of the Medical Service Efim Smirnov (1904-1989). The article highlights biographical information about him.

  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. Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient.

    PubMed

    Benayoun, Liat; Granot, Esther; Rizel, Leah; Allon-Shalev, Stavit; Behar, Doron M; Ben-Yosef, Tamar

    2007-04-01

    Abetalipoproteinemia (ABL) is a rare autosomal recessive metabolic disorder, characterized by the absence of plasma apolipoprotein B-containing lipoproteins and very low levels of plasma triglycerides and cholesterol. ABL is caused by mutations of the MTP gene. We investigated the genetic basis for ABL in a cohort of Israeli families. In Ashkenazi Jewish patients we identified a conserved haplotype and a common MTP mutation, p.G865X, with a carrier frequency of 1:131 in this population. We also report the first case of ABL and additional abnormalities in a Muslim Arab patient, due to a homozygous contiguous gene deletion of approximately 481 kb, including MTP and eight other genes.

  5. A Multiple Case Study of Challenges and Successes Experienced by Founders and Directors of Nature-Based Preschools in the United States

    ERIC Educational Resources Information Center

    Barnett, Alexandra Michaela

    2016-01-01

    Nature-based preschools are defined as educational settings in which children spend three or more hours per school day in natural environments such as woods, meadows, and beaches (Knight, 2013). The purpose of this qualitative, multiple case study was to obtain a deep understanding of the challenges and successes of nature-based preschool (NBP)…

  6. The HNPCC associated MSH2*1906G→C founder mutation probably originated between 1440 CE and 1715 CE in the Ashkenazi Jewish population

    PubMed Central

    Sun, S; Greenwood, C; Thiffault, I; Hamel, N; Chong, G; Foulkes, W

    2005-01-01

    The MSH2*1906G→C mutation was recently shown to be a rare yet highly penetrant mutation leading to colorectal cancer. The mutation was only found among Ashkenazi Jewish individuals and lies on an extended haplotype that is common in that population. This study determined that the mutation probably arose between 11 and 22 generations ago, during the time when the Ashkenazim were living in eastern Europe. PMID:16199548

  7. 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.

  8. 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.

  9. Locating a Prostate Cancer Susceptibility Gene on the X Chromosome by Linkage Disequilibrium Mapping Using Three Founder Populations in Quebec and Switzerland

    DTIC Science & Technology

    2006-09-01

    Sun S, Stoffer SS, Goldgar DE, Romeo G, Houlston RS, Narod SA, Stratton MR and Foulkes WD: A familial non-toxic multinodular thyroid goiter locus...Dis 50: 184-186, 1991. 3*. Druker HA, Kasprzak L, Bégin LR, Jothy S, Narod SA and Foulkes WD: A family with Graves’ disease, multinodular goiter ...Goldgar DE, Romeo G, Houlston RS, Narod SA, Stratton MR and Foulkes WD: A familial non-toxic multinodular thyroid goiter locus maps to chromosome 14q

  10. Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children.

    PubMed

    Ivanov, Ivan S; Azmanov, Dimitar N; Ivanova, Mariya B; Chamova, Teodora; Pacheva, Ilyana H; Panova, Margarita V; Song, Sharon; Morar, Bharti; Yordanova, Ralitsa V; Galabova, Fani K; Sotkova, Iglika G; Linev, Alexandar J; Bitchev, Stoyan; Shearwood, Anne-Marie J; Kancheva, Dalia; Gabrikova, Dana; Karcagi, Veronika; Guergueltcheva, Velina; Geneva, Ina E; Bozhinova, Veneta; Stoyanova, Vili K; Kremensky, Ivo; Jordanova, Albena; Savov, Aleksey; Horvath, Rita; Brown, Matthew A; Tournev, Ivailo; Filipovska, Aleksandra; Kalaydjieva, Luba

    2014-01-01

    Investigation of 31 of Roma patients with congenital lactic acidosis (CLA) from Bulgaria identified homozygosity for the R446* mutation in the PDHX gene as the most common cause of the disorder in this ethnic group. It accounted for around 60% of patients in the study and over 25% of all CLA cases referred to the National Genetic Laboratory in Bulgaria. The detection of a homozygous patient from Hungary and carriers among population controls from Romania and Slovakia suggests a wide spread of the mutation in the European Roma population. The clinical phenotype of the twenty R446* homozygotes was relatively homogeneous, with lactic acidosis crisis in the first days or months of life as the most common initial presentation (15/20 patients) and delayed psychomotor development and/or seizures in infancy as the leading manifestations in a smaller group (5/20 patients). The subsequent clinical picture was dominated by impaired physical growth and a very consistent pattern of static cerebral palsy-like encephalopathy with spasticity and severe to profound mental retardation seen in over 80% of cases. Most patients had a positive family history. We propose testing for the R446* mutation in PDHX as a rapid first screening in Roma infants with metabolic acidosis. It will facilitate and accelerate diagnosis in a large proportion of cases, allow early rehabilitation to alleviate the chronic clinical course, and prevent further affected births in high-risk families.

  11. 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.

  12. Founder's Award, Society for Biomaterials. Sixth World Biomaterials Congress 2000, Kamuela, HI,May 15-20, 2000. Really smart bioconjugates of smart polymers and receptor proteins.

    PubMed

    Hoffman, A S; Stayton, P S; Bulmus, V; Chen, G; Chen, J; Cheung, C; Chilkoti, A; Ding, Z; Dong, L; Fong, R; Lackey, C A; Long, C J; Miura, M; Morris, J E; Murthy, N; Nabeshima, Y; Park, T G; Press, O W; Shimoboji, T; Shoemaker, S; Yang, H J; Monji, N; Nowinski, R C; Cole, C A; Priest, J H; Harris, J M; Nakamae, K; Nishino, T; Miyata, T

    2000-12-15

    Over the past 18 years we have been deeply involved with the synthesis and applications of stimuli-responsive polymer systems, especially polymer-biomolecule conjugates. This article summarizes our work with one of these conjugate systems, specifically polymer-protein conjugates. We include conjugates prepared by random polymer conjugation to lysine amino groups, and also those prepared by site-specific conjugation of the polymer to specific amino acid sites that are genetically engineered into the known amino acid sequence of the protein. We describe the preparation and properties of thermally sensitive random conjugates to enzymes and several affinity recognition proteins. We have also prepared site-specific conjugates to streptavidin with temperature-sensitive polymers, pH-sensitive polymers, and light-sensitive polymers. The preparation of these conjugates and their many fascinating applications are reviewed in this article.

  13. Professor Eugen Cerkovnikov (1904-1985): the founder of the Chemical and Biochemical Institute of the Rijeka University School of Medicine.

    PubMed

    Milin, Cedomila

    2008-01-01

    Professor Eugen Cerkovnikov, PhD (Kamenska, Russia, 1904- Rijeka, Croatia 1985) graduated in chemical technology from the Faculty of Engineering in Zagreb in 1929. His first job was at the School of Medicine in Paris in 1930, and then he moved to Zagreb to the Department of Organic Chemistry of the Faculty of Engineering run by our Nobel Prize winner Vladimir Prelog (1935-1938). There he took his PhD degree with a dissertation on piperidine gamma derivatives. From 1938 to 1947 he was a research associate at an institute established by the pharmaceutical company Kastel (later Pliva). This is when he became a lecturer at the Faculty of Pharmacy in Zagreb and the first director of the Institute of Organic Chemistry, established in 1946/47. In 1948 he became reader, and in 1956 (full) professor. In 1957 he moved to the newly established School of Medicine in Rijeka, and set up the Institute of Chemistry and Biochemistry. He ran the Institute until retirement in 1975. He was the second dean of the Rijeka University School of Medicine and a pioneer of quantum chemistry and medical cybernetics in undergraduate and (post)graduate courses. His scientific work consists of over 200 papers published at home and abroad, 60 professional papers, 20 book reviews, three works of translation, and 27 volumes of lecture notes. In 1958, professor Cerkovnikov established the Croatian Chemical Society and the Rijeka and Istria branches of the nation's Association of Chemists and Chemical Engineers, chairing them until 1974. In addition, he was one of the founding fathers, and the first chair of the Health Culture Studies Association in Rijeka (that preceded today's Croatian Scientific Society for the History of Health Culture), established in 1965.

  14. A concurrent resolution commemorating the 40th anniversary of Earth Day and honoring the founder of Earth Day, the late Senator Gaylord Nelson of the State of Wisconsin.

    THOMAS, 111th Congress

    Sen. Feingold, Russell D. [D-WI

    2010-03-23

    03/23/2010 Referred to the Committee on the Judiciary. (text of measure as introduced: CR S1878) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  15. 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.

  16. 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

  17. Perspectives--A Tribute to Katie Beckett: Advocate for Youth with Disabilities and Founder of "Kids As Self-Advocates" Network (March 9, 1978-May 18, 2012)

    ERIC Educational Resources Information Center

    Oser, Cindy; Whiteman, Jodi

    2012-01-01

    The authors remember the life of Katie Beckett, who was an outspoken advocate for disability rights and inspired the Katie Beckett Waiver Program, which allowed children to continue to be eligible for Medicaid and to have their health care needs provided in the home rather than being forced to be in a hospital or institution. Together, Katie and…

  18. 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.

  19. 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

  20. [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.

  1. 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...

  2. [Prof. Maria Byrdy--Doctor Honoris Causa AMB 1990, the founder of the Chair of Forensic Medicine, the first head of the Department of Forensic Medicine, Medical University of Bialystok in 1954-1984].

    PubMed

    Janica, Jerzy

    2004-01-01

    The paper portrays the scientific, publicist and teaching activities of Prof. M. Byrdy, with special regard to her residence at the Departments of Forensic Medicine in Cracow (1939-1953) and Bialystok (1954-1984).

  3. Dr David Maclagan (1785-1865): distinguished Military Surgeon, President of both the Royal College of Surgeons and Royal College Physicians of Edinburgh, founder of a medical and military dynasty.

    PubMed

    Kaufman, Matthew H

    2006-05-01

    Dr David Maclagan studied medicine in Edinburgh, obtaining the LRCS Edin Diploma in 1804 and graduating with the MD degree in 1805. Because he was too young to enter the army, he spent a year in London, principally at St. George's Hospital, and he gained the MRCS England Diploma in 1807. Then he entered the army as an Assistant Surgeon associated with the 91st Foot Regiment. He served at Walcheren in 1809 and in the Peninsula. Later he was seconded as a Surgeon-Major to the 9th Portuguese Brigade. After his promotion to Physician to the Forces, he superintended the hospital arrangements of the Portuguese Army. Between 1811 and 1814 he sent a series of letters, principally to his wife, giving his personal impressions of his life in the war zone. He also maintained two personal diaries that nominally detailed his activities in the Peninsula between 1812 and 1813. After the end of the fighting he was put on half-pay and returned to Edinburgh. Then he gained the Fellowship of the Royal College of Surgeons of Edinburgh in 1816 and was appointed a Surgeon to the New Town Dispensary. After he established himself in private practice in Edinburgh he became the Honorary Consulting Surgeon to the Dispensary until shortly before his death. He was elected President of the Edinburgh College of Surgeons in 1826-27. He became a Fellow of the Royal College of Physicians of Edinburgh in 1848, and was elected its President in 1856-57. He founded an important medical and military dynasty. Three of his sons joined the medical profession and four served in the army. One of his sons was appointed Archbishop of York. His eldest son followed in his father's footsteps and was also President of both Royal Colleges, of Surgeons and Physicians, in Edinburgh. His widow, Jane, and his seven sons survived him.

  4. Diversification in an Afro-Asian songbird clade (Erythropygia-Copsychus) reveals founder-event speciation via trans-oceanic dispersals and a southern to northern colonization pattern in Africa.

    PubMed

    Voelker, Gary; Peñalba, Joshua V; Huntley, Jerry W; Bowie, Rauri C K

    2014-04-01

    Erythropygia scrub-robins and their allies are distributed throughout Africa, Europe, Southeast Asia, India, Madagascar and the Seychelles. This broad distribution, as well as the distribution of Erythropygia taxa across Africa, presents an interesting opportunity to explore the mechanisms by which this biogeographic distribution was achieved. Multilocus sequence data (3310 base pairs from two mitochondrial and two nuclear genes) were generated for all species of Erythropygia and Cercotrichas scrub-robins, as well as from genera previously shown to render Erythropygia paraphyletic. Using model-based phylogenetic methods and molecular clock dating, we constructed a time-calibrated molecular phylogenetic hypothesis for the lineage. Ancestral area reconstructions were performed on the phylogeny using probabilistic approaches implemented in LaGrange and BioGeoBEARS. Our results confirm that Erythropygia is not monophyletic, and that one of the two Erythropygia clades is more closely related to a clade of Asian and Indian Ocean islands distributed species. Overall, the Erythropygia and allies clade originated in Africa in the late Miocene c. 6.9 Ma. Subsequently, a number of overwater dispersals occurred to include an initial colonization of Southeast Asia, and an ensuing progression of colonizations from Southeast Asia to the Seychelles, from there to Madagascar, and from these Indian Ocean islands back to Southeast Asia. Within the two clades of Erythropygia, ancestral area reconstructions within Africa indicate a Southern Africa origin, with subsequent lineage divergence in each clade indicating northward colonization. Overall, this clade of non-migratory songbirds shows a remarkable number of trans-oceanic colonization events, that were possibly facilitated by wind-driven dispersal; repeated Africa to Asia colonizations, two of which occur in this clade, are exceptionally rare in birds. Also rare is our finding that colonization patterns in Africa indicate a southern to northern progression.

  5. [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.

  6. [Prof. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery at Kyoto University and his achievements in orthopaedic surgery in the Meiji era of Japan (Part 5, Faculty members and training of doctors from Nagoya)].

    PubMed

    Hirotani, Hayato

    2010-09-01

    During the years when Dr. M. Matsuoka was professor of the Department of Orthopaedic Surgery, Kyoto Medical School, Kyoto Imperial University (June, 1907-January, 1914), seven doctors worked as his faculty members and founded the base of the current development and reputation of the Department. After resignation from their academic positions, they served in orthopaedic practice in several areas in Japan where orthopaedic surgery was not well recognized. In addition, Prof. Matsuoka trained three doctors from the Aichi Prefectural Medical College (School of Medicine, Nagoya University) in the orthopaedic practice, including x-ray technique and they contributed to the development of orthopaedic surgery in the areas of Nagoya city and Tokai. Backgrounds and achievements of these ten doctors are described.

  7. [Prof. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements in orthopaedic surgery in the Meiji Era of Japan (part 1: establishment of the department)].

    PubMed

    Hirotani, Hayato

    2005-09-01

    The Department of Orthopaedic and Musculoskeletal Surgery, Graduate School of Medicine, Kyoto University (formerly the Department of Orthopaedic Surgery, Kyoto Medical School, Kyoto Imperial University) was founded by Imperial Ordinance, Article No. 89 issued on April 23, 1906. On May 4, 1906, Dr. Shinichiro Asahara, Assistant Professor of the Department of Surgery, was appointed as the first director of the Department of Orthopaedic Surgery, Kyoto Medical School, Kyoto Imperial University. Dr. Michiharu Matsuoka, Assistant Doctor of the Department of Surgery, Tokyo Medical School, Imperial University of Tokyo, was appointed Assistant Professor of Surgery, Kyoto Medical School, Kyoto Imperial University in March 1901. From August 1903 to May 1906, he studied orthopaedic surgery in Germany and returned on May 5, 1906. Dr. Matsuoka was appointed as the director and chief of the Department on May 13, 1906 and took over Dr. Asahara's position. On June 18, 1906, Dr. Matsuoka started his clinic and began giving lectures on orthopaedic surgery. This was the first department of orthopaedic surgery among the Japanese medical schools. Dr. Matsuoka was appointed as Professor in 1907. He had to overcome several obstacles to establish the medical department of a new discipline that had never existed in Japanese medical schools. This article discusses Dr. Matsuoka's contributions to establishing and developing orthopaedic surgery in Japan in the Meiji-era.

  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.

  9. Dr Edward Macgowan (1795-1860), a long-term pioneer physician in mid-nineteenth century Jerusalem: founder and director of the first modern hospital in the Holy Land.

    PubMed

    Lev, Efraim; Perry, Yaron

    2008-02-01

    At the age of 46, Dr Edward Macgowan, by now a well-established physician, joined the ranks of the London Society for Promoting Christianity among the Jews with the aim of establishing the first modern hospital in Palestine. For the first six months of 1842, Macgowan established his work among the Jerusalem population on a regular basis and managed to establish a close relationship with the Jewish community and some of its leaders in Jerusalem. On 12 December 1844, the Jews' Hospital was opened in Jerusalem and became a source of great pride for the missionaries. Edward Macgowan died in Jerusalem after 18 years of service and was buried in the Protestant cemetery in his beloved city.

  10. 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

  11. Brain Tumor Statistics

    MedlinePlus

    ... About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Press Releases Headlines Newsletter ... About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information ...

  12. 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…

  13. 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.

  14. 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.

  15. 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

  16. Founder's award to Antonios G. Mikos, Ph.D., 2011 Society for Biomaterials annual meeting and exposition, Orlando, Florida, April 13-16, 2011: Bones to biomaterials and back again--20 years of taking cues from nature to engineer synthetic polymer scaffolds.

    PubMed

    Kretlow, James D; Mikos, Antonios G

    2011-09-01

    For biomaterials scientists focusing on tissue engineering applications, the gold standard material is healthy, autologous tissue. Ideal material properties and construct design parameters are thus both obvious and often times unachievable; additional considerations such as construct delivery and the underlying pathology necessitating new tissue yield additional design challenges with solutions that are not evident in nature. For the past nearly two decades, our laboratory and collaborators have aimed to develop both new biomaterials and a better understanding of the complex interplay between material and host tissue to facilitate bone and cartilage regeneration. Various approaches have ranged from mimicking native tissue material properties and architecture to developing systems for bioactive molecule delivery as soluble factors or bound directly to the biomaterial substrate. Such technologies have allowed others and us to design synthetic biomaterials incorporating increasing levels of complexity found in native tissues with promising advances made toward translational success. Recent work focuses on translation of these technologies in specific clinical situations through the use of adjunctive biomaterials designed to address existing pathologies or guide host-material integration.

  17. The Canticle's Song of Sixpence.

    ERIC Educational Resources Information Center

    Work Matters, 1988

    1988-01-01

    Consists of an interview with one of the founders of the Canticle Bakery in Melbourne, Australia. The bakery was developed as a nonprofit venture and provides employment for about 13 young people as well as the founders. Emphasis is placed on quality of product and quality of work life. (CH)

  18. 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…

  19. 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…

  20. Higher establishment success in more diverse groups of pygmy grasshoppers under seminatural conditions.

    PubMed

    Wennersten, Lena; Johansson, Jenny; Karpestam, Einat; Forsman, Anders

    2012-12-01

    Large founder groups and habitat match have been shown to increase the establishment success of reintroduced populations. Theory posits that the diversity of founder groups should also be important, but this has rarely been investigated. Here, experimental introductions of color-polymorphic Tetrix subulata pygmy grasshoppers into outdoor enclosures were used to test whether higher phenotypic diversity promotes establishment success. We show that the number of individuals present one year after introduction increases with color morph diversity in founder groups. Variance in establishment success did not decrease with increasing founder diversity, arguing against an important contribution of sampling effects or evolutionary rescue. Color morphs in T. subulata covary with a suite of other functionally important traits and utilize different resources. The higher establishment success in more diverse founder groups may therefore result, in part, from niche complementarity. Variation in establishment among groups was not associated with differences among source populations in reproductive capacities.

  1. 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

  2. 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

  3. Buberian Learning Groups: Existentialist Philosophy as an Ariadne Thread for Education for Peace--A Final Report.

    ERIC Educational Resources Information Center

    Gordon, Haim

    1983-01-01

    Existentialism holds both a promise and a threat for education. The author draws on philosophical insights to explain why Buberian Learning Groups in Israel, composed of Arabs and Jews, foundered after Israel invaded Lebanon. (PP)

  4. Teaching the Founding of the United States.

    ERIC Educational Resources Information Center

    Berns, Walter

    1985-01-01

    If students are to understand the American Constitution, they must, like the Founders, take political philosophy seriously. Books and essays that college teachers can use to teach about the Declaration of Independence and the Constitution are discussed. (RM)

  5. "Yugoslavia" Branch of the International Astronomical Institute "Isaac Newton"

    NASA Astrophysics Data System (ADS)

    Dimitrijević, Milan S.; Popović, Luka Č.; Simić, Zoran; Jovanović, Predrag; Milovanović, Nenad; Bon, Edi

    2005-10-01

    Isaac Newton Institute of Chile in Eastern Europe and Eurasia and its president and founder Gonzalo Alcaino Barros have been presented as well as the foundation and activities of its "Yugoslavia" branch.

  6. 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)

  7. 78 FR 5251 - National Day of Hope and Resolve, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-24

    ... another. Today, I have sworn an oath to preserve the fundamental freedoms and protections that are the... leave, let them say we did what was required of us, that our words were true to our Founders' dreams...

  8. 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.

  9. 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...

  10. Hoffmeister, Cuno (1892-1968)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    German astronomer, founder of the Sonnenberg Observatory. Discovered thousands of variable stars through repeated photography of the sky and his technique of `fly-spanking', comparing the size of the stellar images to identify changes....

  11. Happy Birthday JCI

    PubMed Central

    Rockman, Howard A.

    2014-01-01

    On the occasion of the ninetieth anniversary of the JCI, I am again humbled by the remarkable insight and passion of our pioneering founders when they created the Journal of Clinical Investigation in 1924. PMID:25271720

  12. An Interview with Dr. Shin'ichi Suzuki at the Talent Education Institute, Matsumoto, Japan, on 18 April 1991.

    ERIC Educational Resources Information Center

    Grilli, Susan; Suzuki, Shin'ichi

    1992-01-01

    Shin-ichi Suzuki, founder of the Talent Education Movement and creator of the Sukuzi Method of musical training, responds to a variety of questions concerning his philosophy of life and lifelong education. (DMM)

  13. Interview at a Small Maine School.

    ERIC Educational Resources Information Center

    Cartwright, Sally

    1991-01-01

    Presents an interview with the founder and director of the Riley School in Maine in which she discusses the school's educational philosophy and practices, curriculum design, and physical plant design. (BB)

  14. 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...  

  15. 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...

  16. Down to Duck Pond Level.

    ERIC Educational Resources Information Center

    Croall, Jonathan

    1978-01-01

    The author talks to the founder of the Center for Village Studies. His name is George Delf, and his concern is with the long-term future of villages for which he has some energetic proposals. (Editor/RK)

  17. 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.

  18. 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.

  19. 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...  

  20. New chromosomal evidence for the origin of Triatoma infestans populations from Brazil.

    PubMed

    Pereira, N P; Alevi, K C C; Rosa, J A; Azeredo-Oliveira, M T V

    2016-08-26

    In this study, the karyometry of different Triatoma infestans populations from different states of Brazil was analyzed and compared with those of a population from Cochabamba. No significant differences were found between the population from Cochabamba and those from Brazil. These results are consistent with the origin of the T. infestans populations of Brazil by a founder effect from Cochabamba. Moreover, these findings also confirm that a founder effect occurred during the dispersal of T. infestans populations in different Brazilian states.

  1. North Korean Foreign Relations in the Post-Cold War World

    DTIC Science & Technology

    2007-04-01

    alienation, and the death of its founder, the “ eternal president” Kim Il Sung. But with its nuclear and missile brinkmanship diplomacy, it has become a...death of its founder, the “ eternal president” Kim Il Sung, a downward spiral of industrial output, food/energy/ hard currency shortages, shrinking...Denuclearization of the Korean Peninsula.” With Kim Dae Jung’s inauguration as ROK president in February 1998, South Korea initiated the Sunshine

  2. Islamic Fundamentalism in Pakistan. Its Characters and Prospects

    DTIC Science & Technology

    1991-01-01

    For although Pakistan was founded as a Muslim homeland, it was not at all the intention of its founder, Muhammad Ali Jinnah , that the state should be...origin: "* The founder of Pakistan, Muhammad ’ Ali Jinnah , was of Isma’ili background; "* Yahya Khan, former Commander in Chief of the Army, and then...more interested in socialist policies or regional issues. Islam entered more fully into the political debate when former Prime Minister Zulfikar Ali

  3. IPB: Predicting an Unpredictable Enemy Why We do it? Why the S2 can’t do it? What the Staff Should

    DTIC Science & Technology

    2007-03-01

    to support the study’s findings. These include the studies of Jeff Hawkins, the founder of Palm Pilot and a student of neuroscience from his book...Hawkins, the founder of Palm Pilot and a student of neuroscience from his book On Intelligence; Richard Heuer, a social psychologist that works for the...that prediction because it involves representing future actions mentally in one’s mind , occurs both unconsciously and consciously. It is an automatic

  4. Iran: U.S. Concerns and Policy Responses

    DTIC Science & Technology

    2014-03-05

    visit to the U.N. General Assembly meetings in New York. In their speeches to the Assembly, both President Obama and Rouhani indicated that the long...style free markets. CIS founder, Amir Abbas Fakhravar, is based in Washington, DC. Co-founder, Arzhang Davoodi, remains in prison in Iran serving a...December 15, 2010, bombing at a mosque in Chahbahar, also in Baluchistan, that killed 38. Kurdish Armed Groups: Free Life Party (PJAK) An armed Kurdish

  5. Seventeenth-century European origins of hereditary diseases in the Saguenay population (Quebec, Canada).

    PubMed

    Heyer, E; Tremblay, M; Desjardins, B

    1997-04-01

    For over three decades much research has been devoted to the identification of founders who could have been the first carriers of different deleterious genes in the French Canadian population. In some cases this research led to an investigation of the European origins of these founders. Using up-to-date data on genealogical records of 673 probands (6 hereditary diseases) and 99 control group individuals born in the Saguenay region (Quebec, Canada), we show that it is difficult to identify a precise region where a deleterious gene could have originated. By taking several key factors into consideration (founders' genetic contribution, level of commonness, sex, birth year), we found many possible candidates for each disease, leading to various regions of origin in France (Aunis, Maine, Normandie, Orléanais, Perche, and other provinces) or outside France (British Isles, other European countries). Our results also showed notable differences between the origins of male and female founders. Furthermore, all founders common to at least 95% of the probands of a given disease were also common to 95% of the probands of at least one other disease; among these founders 29 were common to 95% or more of the probands of each group (including the control group).

  6. 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.

  7. The spectrum of BRCA1 and BRCA2 mutations in breast cancer patients in the Bahamas.

    PubMed

    Akbari, M R; Donenberg, T; Lunn, J; Curling, D; Turnquest, T; Krill-Jackson, E; Zhang, S; Narod, S A; Hurley, J

    2014-01-01

    We sought to identify the full range of founder mutations in BRCA1 and BRCA2 in the Bahamas and to estimate the proportion of all BRCA1 and BRCA2 mutations that are accounted for by founder mutations. We studied 214 Bahamian women with invasive breast cancer, unselected for age or family history. A founder mutation had previously been identified in 49 patients. We conducted full sequencing of the BRCA1 and BRCA2 genes and multiplex ligation-dependent probe amplification (MLPA) for 156 patients. A novel founder mutation in BRCA2 (exon 17 818delA) was seen in four different patients and five other unique mutations in BRCA1 and BRCA2, including a large deletion (exons 8-9) in BRCA1. In total, a mutation was seen in 58 of the 214 patients (27%); 92% of carriers carried one of the seven founder mutations. Approximately 27% of unselected cases of breast cancer in the Bahamian population are attributable to a mutation in BRCA1 or BRCA2, a prevalence which far exceeds that of any other country. The majority of women who carry a mutation in the Bahamas, carry one of the seven founder mutations, making it possible to offer genetic testing to all women at risk for breast cancer in the Bahamas.

  8. A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube enlargement in Drosophila

    PubMed Central

    Menon, Sree Devi; Osman, Zalina; Chenchill, Kho; Chia, William

    2005-01-01

    In Drosophila, myoblasts are subdivided into founders and fusion-competent myoblasts (fcm) with myotubes forming through fusion of one founder and several fcm. Duf and rolling pebbles 7 (Rols7; also known as antisocial) are expressed in founders, whereas sticks and stones (SNS) is present in fcm. Duf attracts fcm toward founders and also causes translocation of Rols7 from the cytoplasm to the fusion site. We show that Duf is a type 1 transmembrane protein that induces Rols7 translocation specifically when present intact and engaged in homophilic or Duf–SNS adhesion. Although its membrane-anchored extracellular domain functions as an attractant and is sufficient for the initial round of fusion, subsequent fusions require replenishment of Duf through cotranslocation with Rols7 tetratricopeptide repeat/coiled-coil domain-containing vesicles to the founder/myotube surface, causing both Duf and Rols7 to be at fusion sites between founders/myotubes and fcm. This implicates the Duf–Rols7 positive feedback loop to the occurrence of fusion at specific sites along the membrane and provides a mechanism by which the rate of fusion is controlled. PMID:15955848

  9. Bayesian inferences on the recent island colonization history by the bird Zosterops lateralis lateralis.

    PubMed

    Estoup, A; Clegg, S M

    2003-03-01

    The founding of new populations by small numbers of colonists has been considered a potentially important mechanism promoting evolutionary change in island populations. Colonizing species, such as members of the avian species complex Zosterops lateralis, have been used to support this idea. A large amount of background information on recent colonization history is available for one Zosterops subspecies, Z. lateralis lateralis, providing the opportunity to reconstruct the population dynamics of its colonization sequence. We used a Bayesian approach to combine historical and demographic information available on Z. l. lateralis with genotypic data from six microsatellite loci, and a rejection algorithm to make simultaneous inferences on the demographic parameters describing the recent colonization history of this subspecies in four southwest Pacific islands. Demographic models assuming mutation-drift equilibrium or a large number of founders were better supported than models assuming founder events for three of four recently colonized island populations. Posterior distributions of demographic parameters supported (i) a large stable effective population size of several thousands individuals with point estimates around 4000-5000; (ii) a founder event of very low intensity with a large effective number of founders around 150-200 individuals for each island in three of four islands, suggesting the colonization of those islands by one flock of large size or several flocks of average size; and (iii) a founder event of higher intensity on Norfolk Island with an effective number of founders around 20 individuals, suggesting colonization by a single flock of moderate size. Our inferences on demographic parameters, especially those on the number of founders, were relatively insensitive to the precise choice of prior distributions for microsatellite mutation processes and demographic parameters, suggesting that our analysis provides a robust description of the recent

  10. 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

  11. Genetic diversity of laboratory gray short-tailed opossums (Monodelphis domestica): effect of newly introduced wild-caught animals.

    PubMed

    van Oorschot, R A; Williams-Blangero, S; VandeBerg, J L

    1992-06-01

    The colony of gray, short-tailed opossums (Monodelphis domestica) at the Southwest Foundation for Biomedical Research, the primary supplier of this species for research purposes, was founded with nine animals trapped in 1978 in the state of Pernambuco, Brazil. Since 1984, 14 newly acquired founders from the state of Paraiba, Brazil have contributed to the gene pool of the colony. The animals from Paraiba and their descendants are significantly larger than the founders from Pernambuco and their descendants. The two groups also differ significantly in several measurements of morphologic traits. The changes in proportional contribution of each founder to the colony, and changes in inbreeding coefficients during the colony's history, are evaluated. Using previously established markers and three newly identified markers (ACP2, APRT, and DIA1), we show that the Paraiba-derived animals differ significantly from the original founders in allele frequencies and heterozygosity. The genetic diversity of the colony has been substantially increased by acquisition of the new founders from Paraiba. The colony is highly polymorphic, with 22.2% of loci surveyed by protein electrophoresis being variable. We conclude that the genetic differences between populations and among projects within the colony should be considered in future colony management procedures and in selection of experimental subjects.

  12. 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.

  13. Factors involved in the prognosis of equine laminitis in the UK.

    PubMed

    Cripps, P J; Eustace, R A

    1999-09-01

    The significance of clinical and radiological parameters as prognostic indicators for laminitis, 'founder' and 'sinking syndrome' was studied using case records of 216 horses and ponies. Five animals were destroyed without treatment and were not included in the results of the study. One hundred and sixty-two (77%) animals returned to athletic soundness; 7 animals (3%) did not regain full athletic function, 42 animals (20%) died or were destroyed. Cases were assigned to 4 groups on the basis of initial clinical examination alone. These groups were laminitis, acute founder, 'sinker' and chronic founder. This grouping was found in itself to be the most important prognostic parameter which was studied. Stepwise regression analysis of the data from animals by group indicated that the radiological measurement of founder distance, was the most significant radiological prognostic measurement for acute founder cases. Less significant prognostic parameters were the severity of lameness, rotation angles, the presence of solar prolapse, and the number of feet affected. The height of the animal at the withers was not significantly related to outcome. The prognosis for horses was not significantly different from that for ponies.

  14. Using the emerging Collaborative Cross to probe the immune system

    PubMed Central

    Phillippi, Jason; Xie, Yuying; Miller, Darla R; Bell, Timothy A; Zhang, Zhaojun; Lenarcic, Alan B; Aylor, David L; Krovi, S Harsha; Threadgill, David W.; de Villena, Fernando Pardo-Manuel; Wang, Wei; Valdar, William; Frelinger, Jeffrey A.

    2014-01-01

    The Collaborative Cross (CC) is an emerging panel of recombinant inbred mouse strains. Each strain is genetically distinct but all descended from the same eight inbred founders. In 66 strains from incipient lines of the CC (pre-CC), as well as the 8 CC founders and some of their F1 offspring, we examined subsets of lymphocytes and antigen-presenting cells. We found significant variation among the founders, with even greater diversity in the pre-CC. Genome-wide association using inferred haplotypes detected highly significant loci controlling B-to-T cell ratio, CD8 T-cell numbers, CD11c and CD23 expression. Comparison of overall strain effects in the CC founders with strain effects at QTL in the pre-CC revealed sharp contrasts in the genetic architecture of two traits with significant loci: variation in CD23 can be explained largely by additive genetics at one locus, whereas variation in B-to-T ratio has a more complex etiology. For CD23, we found a strong QTL whose confidence interval contained the CD23 structural gene Fcer2a. Our data on the pre-CC demonstrate the utility of the CC for studying immunophenotypes and the value of integrating founder, CC, and F1 data. The extreme immunophenotypes observed could have pleiotropic effects in other CC experiments. PMID:24195963

  15. 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.

  16. Heritable Targeted Inactivation of Myostatin Gene in Yellow Catfish (Pelteobagrus fulvidraco) Using Engineered Zinc Finger Nucleases

    PubMed Central

    Li, Kui; Xu, Zhiqiang; Liang, Dong; Li, Jingyun; Li, Junbo; Jia, Wenshuang; Li, Yuehua; Dong, Xiaohua; Cao, Shasha; Wang, Xiaoxiao; Pan, Jianlin; Zhao, Qingshun

    2011-01-01

    Yellow catfish (Pelteobagrus fulvidraco) is one of the most important freshwater aquaculture species in China. However, its small size and lower meat yield limit its edible value. Myostatin (MSTN) is a negative regulator of mammalian muscle growth. But, the function of Mstn in fish remains elusive. To explore roles of mstn gene in fish growth and create a strain of yellow catfish with high amount of muscle mass, we performed targeted disruption of mstn in yellow catfish using engineered zinc-finger nucleases (ZFNs). Employing zebrafish embryos as a screening system to identify ZFN activity, we obtained one pair of ZFNs that can edit mstn in yellow catfish genome. Using the ZFNs, we successfully obtained two founders (Founder July29-7 and Founder July29-8) carrying mutated mstn gene in their germ cells. The mutated mstn allele inherited from Founder July29-7 was a null allele (mstnnju6) containing a 4 bp insertion, predicted to encode function null Mstn. The mutated mstn inherited from Founder July29-8 was a complex type of mutation (mstnnju7), predicted to encode a protein lacking two amino acids in the N-terminal secretory signal of Mstn. Totally, we obtained 6 mstnnju6/+ and 14 mstnnju7/+ yellow catfish. To our best knowledge, this is the first endogenous gene knockout in aquaculture fish. Our result will help in understanding the roles of mstn gene in fish. PMID:22194943

  17. 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

  18. 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

  19. Estimating ethnic admixture from pedigree data.

    PubMed

    Sinsheimer, Janet S; Plaisier, Christopher L; Huertas-Vazquez, Adriana; Aguilar-Salinas, Carlos; Tusie-Luna, Teresa; Pajukanta, Päivi; Lange, Kenneth

    2008-03-01

    This paper introduces a likelihood method of estimating ethnic admixture that uses individuals, pedigrees, or a combination of individuals and pedigrees. For each founder of a pedigree, admixture proportions are calculated by conditioning on the pedigree-wide genotypes at all ancestry-informative markers. These estimates are then propagated down the pedigree to the nonfounders by a simple averaging process. The large-sample standard errors of the founders' proportions can be similarly transformed into standard errors for the admixture proportions of the descendants. These standard errors are smaller than the corresponding standard errors when each individual is treated independently. Both hard and soft information on a founder's ancestry can be accommodated in this scheme, which has been implemented in the genetic software package Mendel. The utility of the method is demonstrated on simulated data and a real data example involving Mexican families of mixed Amerindian and Spanish ancestry.

  20. 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.

  1. Pre-Durkheim suicidology.

    PubMed

    Goldney, R D; Schioldann, J A

    2000-01-01

    Durkheim is generally regarded as the founder of the scientific study of suicide. However, even a cursory review of 18th- and 19th-century literature reveals an increasingly sophisticated scientific approach to suicide, culminating in the encyclopedic research of Morselli in 1879 and the critical review of Tuke in 1892, works that lose nothing in comparison with Durkheim's Le Suicide of 1897. This review, while in no way drawing Durkheim's role as a founder of scientific sociology into question, indicates that his position in regard to the study of suicide does warrant reconsideration.

  2. 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."

  3. To understand what happens to the foods that you and I eat. An interview with Dr. Vay Liang Go. Interview by Martin E. Fernandez-Zapico.

    PubMed

    Go, Vay Liang

    2006-01-01

    Vay Liang Go is an internationally renowned pancreatic scientist and clinical investigator. Doctor Go's work was fundamental for the understanding of the neuro-hormonal control of gastrointestinal and pancreatic function and metabolism. Additionally, he contributed enormously to the pancreatic community by being one of the founders of the American Pancreatic Association and also co-founder of the journal Pancreas. He trained a large number of fellows and junior faculties, many of whom now are national and international opinion leaders in gastroenterology and pancreatology. In this interview, Doctor Go gives us his views and shares his professional experiences in pancreatic research.

  4. 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.

  5. A “Fille du Roy” Introduced the T14484C Leber Hereditary Optic Neuropathy Mutation in French Canadians

    PubMed Central

    Laberge, Anne-Marie; Jomphe, Michèle; Houde, Louis; Vézina, Hélène; Tremblay, Marc; Desjardins, Bertrand; Labuda, Damian; St-Hilaire, Marc; Macmillan, Carol; Shoubridge, Eric A.; Brais, Bernard

    2005-01-01

    The predominance of the T14484C mutation in French Canadians with Leber hereditary optic neuropathy is due to a founder effect. By use of genealogical reconstructions of maternal lineages, a woman married in Quebec City in 1669 is identified as the shared female ancestor for 11 of 13 affected individuals, who were previously not known to be related. These individuals carry identical mitochondrial haplogroups. The current geographic distribution of French Canadian cases overlaps with that of the founder’s female descendants in 1800. This is the first example of genealogical reconstruction to identify the introduction of a mitochondrial mutation by a woman in a founder population. PMID:15954041

  6. 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.

  7. American Philanthropic Studies: The Chicago School of Civics and Philanthropy (1903-1920)

    ERIC Educational Resources Information Center

    Seely, Dagmar

    2014-01-01

    Graham Taylor was a leader in the movement for schools of civics and philanthropy. As founder of the Chicago School of Civics and Philanthropy, Taylor served as President and Professor. The study focuses on the development of the study of philanthropy through following the pedagogy of Graham Taylor beginning with his early efforts during the late…

  8. Oneida Cockrell: Pioneer in the Field of Early Childhood Education

    ERIC Educational Resources Information Center

    Simpson, Jean

    2012-01-01

    In this article the author profiles Oneida Cockrell, a pioneer in the field of early childhood education. She was the founder and director of the Garden Apartments Nursery School and Kindergarten, located in the prestigious Michigan Boulevard Garden Apartments building (commonly known as the Rosenwald Apartments) in Chicago's West Hyde Park…

  9. Interview with David Moore

    ERIC Educational Resources Information Center

    Rossman, Allan; Dietz, E. Jacquelin; Moor, David

    2013-01-01

    David Moore is Professor Emeritus of Statistics at Purdue University. He served as the first President of the International Association for Statistical Education (IASE) from 1993-1995 and as President of the American Statistical Association (ASA) in 1998. He is a Fellow of the ASA and of the IMS and was awarded the ASA's Founders Award in…

  10. 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…

  11. Living on the Future Edge: Windows on Tomorrow

    ERIC Educational Resources Information Center

    Jukes, Ian; McCain, Ted; Crockett, Lee

    2010-01-01

    "Living on the Future Edge" challenges school leaders to rethink longstanding paradigms and transform pedagogy for tomorrow's learners. Apple Computer, Inc. co-founder Steve Wozniak's foreword underscores the overwhelming need to adjust traditional instruction to fit today's high-tech world. The book explores this new landscape and…

  12. Stop the Insanity! It Takes a Team to Leave No Child Behind

    ERIC Educational Resources Information Center

    Butzin, Sarah M.

    2004-01-01

    Who says learning always has to be drudgery? Sarah Butzin, the founder of the Institute for School Innovation, proposes "triangulated learning" as a way to give children time to play and develop, even as they pursue high standards. Triangulation is a metaphor for strength. A triangulated learning system taps the power of three to meet…

  13. Special Report: Personal Transformations. Moving from Violence to Peace

    DTIC Science & Technology

    2007-04-01

    Chairman, PFC Energy, Washington, D.C. • María otero (Vice Chair), President, ACCION International, Boston, Mass. • Betty f. Bumpers, Founder and...opportunity to analyze his life in moral terms and listen to what God’s plan for him might be. For Shaftary, it felt like a gradual cleansing process: “I

  14. What Students Can Learn from Steve Jobs. Footnotes. Volume 16, Number 08

    ERIC Educational Resources Information Center

    Husick, Lawrence

    2011-01-01

    A few days ago, Steve Jobs, the rockstar founder and Chief Executive Officer of Apple, Inc. resigned from his job to become Chairman of the Board, instead. For more than ten years, Mr. Jobs has been paid one dollar a year to run what has become the most valuable company in the world. From his first partner, Steve Wozniak, to the small team of…

  15. On the Importance of Subject Matter in Mathematics Education: A Conversation with Erich Christian Wittmann

    ERIC Educational Resources Information Center

    Akinwunmi, Kathrin; Höveler, Karina; Schnell, Susanne

    2014-01-01

    Erich Christian Wittmann is one of the primary founders of mathematics education research as an autonomous field of work and research in Germany. The interview presented here reflects on his role in promoting mathematics education as a design science. The interview addresses the following topics: (1) The importance of subject matter in…

  16. Dame Cicely Saunders: An Omega Interview.

    ERIC Educational Resources Information Center

    Kastenbaum, Robert

    1993-01-01

    Presents interview with Dame Cicely Saunders, founder of international hospice care movement. Saunders describes her background and experiences that led her to form the hospice movement and discusses the need for pain control for terminally ill patients. Saunders also notes her opposition to euthanasia and physician-assisted suicide. (NB)

  17. Family of Origin and Career Counseling: An Interview with Robert Chope

    ERIC Educational Resources Information Center

    Lara, Tracy

    2007-01-01

    Robert Chope is a professor of counseling at San Francisco State University, where he coordinates the Career Counseling Program. He is also the founder of the Career and Personal Development Institute in San Francisco, a practice that he has had for more than 25 years. Dr. Chope received his PhD from the University of Minnesota, Department of…

  18. The Psychological Record: Reaffirming the Past and Embracing the Future

    ERIC Educational Resources Information Center

    Rehfeldt, Ruth Anne

    2007-01-01

    In providing an outlet for manuscripts from all areas of scientific psychology, it was the founders' intentions that authors would experience a more rapid turn-around from submission to publication than was the case with other general psychology journals at the time. Despite difficulties created by World War II, "The Psychological Record" remained…

  19. B. F. Skinner's Contributions to Applied Behavior Analysis

    ERIC Educational Resources Information Center

    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…

  20. Montessori for All: Magnolia Montessori

    ERIC Educational Resources Information Center

    EDUCAUSE, 2015

    2015-01-01

    The founders of Montessori For All, which opened Magnolia Montessori--a PK-8 public charter school in Austin, Texas--created a new school model that blends the best of authentic Montessori schooling (hands-on and self-directed learning) with best practices from high-performing charter schools (basic skills mastery to excel on standardized tests…

  1. Structural disputes

    NASA Astrophysics Data System (ADS)

    Donald, Athene

    2013-06-01

    In March this year, the author of a well-regarded science website was revealed to be - wait for it - a woman. The identification of Elise Andrew as the founder of the provocatively titled Facebook page "I Fucking Love Science" was greeted with astonishment, tinged in some cases with outrage.

  2. 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…

  3. Using Authentic Literature to Develop Challenging and Integrated Curriculum

    ERIC Educational Resources Information Center

    Ciecierski, Lisa M.; Bintz, William P.

    2015-01-01

    Dr. William Alexander, a noted curriculum authority and a central founder of the middle school movement, shared in a presentation in 1963 that teachers must have a goal of stimulating a "love for learning, an attitude of inquiry, a passion for truth and beauty, a questioning of mind." He asserted, "Learning the right answers is not…

  4. Lessons from Afar: A Review of www.daisakuikeda.org, Official Website of Daisaku Ikeda

    ERIC Educational Resources Information Center

    Arauz, Luis

    2012-01-01

    Daisaku Ikeda (1928- ) is a Buddhist leader, peace builder, school founder, and poet. His own biography and lifework provide a model for how one can transform adversity into alternative opportunities for some of the most disenfranchised students. Scrutinizing Ikeda's official website (www.daisakuikeda.org) reveals an extensive collection of his…

  5. Explorations in Creativity: An Interview with Mark Runco

    ERIC Educational Resources Information Center

    Henshon, Suzanna E.

    2010-01-01

    Mark Runco is the Torrance Professor of Creative Studies and Gifted Education at the University of Georgia. He is also the Director of the Torrance Center, and is the founder and editor of the "Creativity Research Journal." His other editorial work includes the "Creativity" book series and the "Encyclopedia of Creativity." This article presents an…

  6. A Retrospective Appraisal of 15 Years' Proceedings of the Hungarian Research Student Association

    ERIC Educational Resources Information Center

    Revesz, Tamas; Olah, Mate

    2013-01-01

    In 1996 the Hungarian Research Student Association (HRSA) was founded. Since then more than 6000 young, talented researchers have belonged to the Association. The founders set two principal aims: (1) to support the gifted and the most promising high school students and (2) to establish an active community. The movement has grown through the work…

  7. 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.

  8. Gender Tracking and Student Choice: Case Study of a Girls' Vocational High School, 1911-1978.

    ERIC Educational Resources Information Center

    Green, Nancy

    The Lucy Flower Technical High School was the only Chicago public high school exclusively for girls. Its founders' goal was to train young women both for sex-segregated employment and for their "primary function" as housewives. The form this aim took in practice and the response to the school over time by Chicago's young women offer…

  9. The GPO and the Depository Library Program as Structured Are Needed: Views of a Selective Depository Librarian.

    ERIC Educational Resources Information Center

    Walshak, Lynn G.

    1998-01-01

    Addresses perceived problems of the Federal Depository Library Program (FDLP) and the Government Printing Office (GPO) relative to a foundering program, electronic capabilities, costs to participating libraries, inefficient service, and accountability requirements. Unfavorable images have resulted and have been used by advocacy groups to bring the…

  10. Riding the First-Year Roller Coaster

    ERIC Educational Resources Information Center

    Moir, Ellen

    2013-01-01

    A teacher's first year of teaching can feel like a sink-or-swim experience. Instead of making steady progress toward becoming a great teacher, in their first year, many teachers become overwhelmed by the daily demands of their own classrooms. As founder and CEO of New Teacher Center, an organization focused on understanding and meeting the…

  11. Genetic diversity in captive and wild Matschie's tree kangaroo (Dendrolagus matschiei) from Huon Peninsula, Papua New Guinea, based on mtDNA control region sequences.

    PubMed

    McGreevy, Thomas J; Dabek, Lisa; Gomez-Chiarri, Marta; Husband, Thomas P

    2009-05-01

    The Association of Zoos and Aquariums (AZA) Matschie's tree kangaroo (Dendrolagus matschiei) population is at a critical point for assessing long-term viability. This population, established from 19 genetically uncharacterized D. matschiei, has endured a founder effect because only four individuals contributed the majority of offspring. The highly variable mitochondrial DNA (mtDNA) control region was sequenced for five of the female-founders by examining extant representatives of their maternal lineage and compared with wild (n = 13) and captive (n = 18) D. matschiei from Papua New Guinea (PNG). AZA female-founder D. matschiei control region haplotype diversity was low, compared with captive D. matschiei held in PNG. AZA D. matschiei have only two control region haplotypes because four out of five AZA female-founder D. matschiei had an identical sequence. Both AZA haplotypes were identified among the 17 wild and captive D. matschiei haplotypes from PNG. Genomic DNA extracted from wild D. matschiei fecal samples was a reliable source of mtDNA that could be used for a larger scale study. We recommend a nuclear DNA genetic analysis to more fully characterize AZA D. matschiei genetic diversity and to assist their Species Survival Plan((R)). An improved understanding of D. matschiei genetics will contribute substantially to the conservation of these unique animals both in captivity and the wild.

  12. Daring to Care: The Role of Culturally Relevant Care in Mentoring Black and Latino Male High School Students

    ERIC Educational Resources Information Center

    Watson, Wanda; Sealey-Ruiz, Yolanda; Jackson, Iesha

    2016-01-01

    This study seeks to challenge the uni-dimensional way care in school is written about by highlighting an often overlooked aspect of care--the kind that students do for each other. Data is drawn from focus groups conducted with the youth participants and founder of Umoja Network for Young Men (UMOJA), an all-male, school-based mentoring program for…

  13. The Keys to the White House: Prediction for 2008

    ERIC Educational Resources Information Center

    Lichtman, Allan

    2008-01-01

    The winds of political change are blowing through America in 2008 and will sweep the party in power from the White House next November. That is the verdict of the Keys to the White House, a prediction system that the author developed in collaboration with Vladimir Keilis-Borok, founder of the International Institute of Earthquake Prediction Theory…

  14. The Keys to the White House: Prediction for 2012

    ERIC Educational Resources Information Center

    Lichtman, Allan

    2012-01-01

    Conventional pundits, pollsters, and forecasters are focused on whether the economy will improve sufficiently in 2012 for President Barack Obama to gain reelection. The Keys to the White House, a prediction system that the author developed in collaboration with Vladimir Keilis-Borok, founder of the International Institute of Earthquake Prediction…

  15. 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…

  16. Memories Are Made of This

    ERIC Educational Resources Information Center

    Chang, Christine

    2010-01-01

    In this article, the author shares her memories of Sally Smith, the founder of The Lab School of Washington, where she works as the director of the Occupational Therapy. When the author first met Smith, Smith asked her what brought her to The Lab School at that point in her career. She told Smith that her background was rather eclectic, since she…

  17. 78 FR 13054 - Announcement of the Board of Directors for the National Environmental Education Foundation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... Cousteau, Co-Founder and CEO, EarthEcho International Manuel Alberto Diaz, Partner, Lydecker Diaz, L.L.P... was Vice President of Alinda Capital Partners since 2011, Consultant of Global Water Challenge since... in History from Yale University. She speaks Spanish, French and Mandarin Chinese. Lives with...

  18. Rediscovering Froebel: A Call to Re-Examine His Life and Gifts

    ERIC Educational Resources Information Center

    Manning, John P.

    2005-01-01

    This article examines the life of Friedrich Froebel, the founder of the kindergarten movement and his first 10 "gifts to children." The author suggests that Froebel's philosophy of German Romanticism caused the waning use of his methods. He continues to state that Froebel's development of instructional material and structured play-based curricula…

  19. Face to Face with Distance Education.

    ERIC Educational Resources Information Center

    Dhanarajan, Gajaraj

    1997-01-01

    Begins with a tribute to Professor G. Ram Reddy (founder of Indira Gandhi National Open University), then focuses on the challenges for India of education in the coming decades. Highlights include global problems that future generations will inherit; educational investment needs; a new group of educational clients; skills needed in the 21st…

  20. Making Distance Education Borderless.

    ERIC Educational Resources Information Center

    Srisa-An, Wichit

    1997-01-01

    Begins with a tribute to Professor G. Ram Reddy (founder of Indira Gandhi National Open University), then focuses on enhancing the role of open universities in providing borderless distance education. Highlights include the need for open distance-education; philosophy and vision; the distance teaching system; the role of information technology;…