Effective Gene Therapy of Mice with Congenital Erythropoietic Porphyria Is Facilitated by a Survival Advantage of Corrected Erythroid Cells

PubMed Central

Robert-Richard, Elodie; Moreau-Gaudry, François; Lalanne, Magalie; Lamrissi-Garcia, Isabelle; Cario-André, Muriel; Guyonnet-Dupérat, Véronique; Taine, Laurence; Ged, Cécile; de Verneuil, Hubert

2008-01-01

Achieving long-term expression of a therapeutic gene in a given hematopoietic lineage remains an important goal of gene therapy. Congenital erythropoietic porphyria (CEP) is a severe autosomal-recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. We used a recently obtained murine model to check the feasibility of gene therapy in this disease. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells (HSCs) from Urosmut248 mice resulted in a complete and long-term enzymatic, metabolic, and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells. These results demonstrate that the cure of this mouse model of CEP at a moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified hematopoietic stem cells. PMID:18179890

Successful and safe treatment of hypertrichosis by high-intensity pulses of noncoherent light in a patient with hepatoerythropoietic porphyria.

PubMed

García-Bravo, María; López-Gómez, Sara; Segurado-Rodríguez, María-Agustina; Morán-Jiménez, María-José; Méndez, Manuel; de Salamanca, Rafael Enríquez; Fontanellas, Antonio

2004-08-01

Hypertrichosis is a common feature in cutaneous porphyrias, characterized by high accumulation of photoreactive porphyrins. Photothermolysis induced by noncoherent light (755-1200 nm) and energy fluence of 42 J/cm(2) was applied to a patient with hepatoerythropoietic porphyria. Hypertrichosis was almost completely removed after seven sessions without development of skin lesions.

Environmental chemical exposures and disturbances of heme synthesis.

PubMed Central

Daniell, W E; Stockbridge, H L; Labbe, R F; Woods, J S; Anderson, K E; Bissell, D M; Bloomer, J R; Ellefson, R D; Moore, M R; Pierach, C A; Schreiber, W E; Tefferi, A; Franklin, G M

1997-01-01

Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria. PMID:9114276

PBG urine test

MedlinePlus

... test. Alternative Names Porphobilinogen test; Porphyria - urine; PBG Images Male urinary system References Fuller SJ, Wiley JS. Heme biosynthesis and its disorders: porphyrias and sideroblastic ...

Inherited disorders in the Afrikaner population of southern Africa. Part I. Historical and demographic background, cardiovascular, neurological, metabolic and intestinal conditions.

PubMed

Botha, M C; Beighton, P

1983-10-08

Certain genetic disorders occur with unusually high frequency in the Afrikaner population of southern Africa. Conditions of this type (reviewed in Part I of this article) include familial hypercholesterolaemia, progressive familial heart block, Huntington's chorea, porphyria variegata, Gaucher's disease, cystic fibrosis and familial colonic polyposis. This genetic situation is explicable to some extent on the basis of the demographic development of the Afrikaner population during the 14 generations since the arrival of the first immigrants from Holland more than 330 years ago.

Markers for vulnerability in acute porphyria. A hypothesis paper.

PubMed

Thunell, S; Andersson, C; Carlmark, B; Floderus, Y; Grönqvist, S O; Harper, P; Henrichson, A; Lindh, U

1995-04-01

Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin concentration. This may mirror a role of the cobalamin-folate system in the acute porphyric process.

Porphyrins and Porphyria Diagnosis

MedlinePlus

... diagnosis The porphyrias are caused by deficiencies of enzymes of the heme biosynthetic pathway. This pathway, like ... heme. Heme is essential for life, and each enzyme is also essential, because it is responsible for ...

American Porphyria Foundation

MedlinePlus

... helping us all connect with each other." ~ Amy Rose Burke, PCT “APF is not only a support ... Darnisha Davenport Liz Cooke Nicole Clarke Louise Coomber Rose and Colin ~ Living with Porphyria ~ Video Jessi Brill ...

Acute Intermittent Porphyria (AIP)

MedlinePlus

... the Healthcare Professionals area of our site. PBS Documentary AIP Diagnosis Stories **Diagnostic Testing for the Acute ... be administered only by physicians experienced in the management of porphyrias in a hospital setting. Panhematin is ...

Diet and Nutrition in Porphyria

MedlinePlus

... the APF You are here Home Diet and Nutrition A proper diet is important to all individuals, ... alter food intake. Therefore, attention to diet and nutrition is important in almost any disease. Porphyrias are ...

Porphyrin Test: MedlinePlus Lab Test Information

MedlinePlus

... cause skin symptoms when you are exposed to sunlight Some porphyrias affect both the nervous system and ... Hallucinations Symptoms of cutaneous porphyria include: Oversensitivity to sunlight Blisters on skin exposed to sunlight Redness and ...

Weight Loss & Acute Porphyria

MedlinePlus

... Nicole Castelano Gregary Edwards Megan Parrish ~ How the dog I didn't want became the dog I'd always dreamed of Darnisha Davenport Liz ... or through the site for commercial or public purposes. The American Porphyria Foundation (APF) Tax Forms 990 ...

Porphyria Treatment Options

MedlinePlus

... Nicole Castelano Gregary Edwards Megan Parrish ~ How the dog I didn't want became the dog I'd always dreamed of Darnisha Davenport Liz ... or through the site for commercial or public purposes. The American Porphyria Foundation (APF) Tax Forms 990 ...

Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias.

PubMed

Stubenhaus, Bradford M; Dustin, John P; Neverett, Emily R; Beaudry, Megan S; Nadeau, Leanna E; Burk-McCoy, Ethan; He, Xinwen; Pearson, Bret J; Pellettieri, Jason

2016-05-31

Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias - decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis.

Glucose Effect in the Acute Porphyrias

MedlinePlus

... Nicole Castelano Gregary Edwards Megan Parrish ~ How the dog I didn't want became the dog I'd always dreamed of Darnisha Davenport Liz ... or through the site for commercial or public purposes. The American Porphyria Foundation (APF) Tax Forms 990 ...

Porphyria

MedlinePlus

... Hift RJ. The porphyrias. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 210. Review Date 2/1/2017 Updated by: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.

PubMed

Yasuda, Makiko; Gan, Lin; Chen, Brenden; Kadirvel, Senkottuvelan; Yu, Chunli; Phillips, John D; New, Maria I; Liebow, Abigail; Fitzgerald, Kevin; Querbes, William; Desnick, Robert J

2014-05-27

The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias.

Molecular analysis reveals a high mutation frequency in the first untranslated exon of the PPOX gene and largely excludes variegate porphyria in a subset of clinically affected Afrikaner families.

PubMed

Kotze, M J; De Villiers, J N; Groenewald, J Z; Rooney, R N; Loubser, O; Thiart, R; Oosthuizen, C J; van Niekerk, M M; Groenewald, I M; Retief, A E; Warnich, L

1998-10-01

A subset of probands from 11 South African families with clinical and/or biochemical features of variegate porphyria (VP), but without the known protoporphyrinogen oxidase (PPOX) gene defects identified previously in the South African population, were subjected to mutation analysis. Disease-related mutation(s) could not be identified after screening virtually the entire PPOX gene by heteroduplex single-strand conformation polymorphism analysis (HEX-SSCP), although three new sequence variants were detected in exon 1 of the gene in three normal controls. The presence of these single base changes at nucleotide positions 22 (C/G), 27 (C/A) and 127 (C/A), in addition to the known exon 1 polymorphisms I-26 and I-150, indicates that this untranslated region of the PPOX gene is particularly mutation-prone. Furthermore, microsatellite markers flanking the PPOX and alpha-1 antitrypsin (PI) gene, on chromosomes 1 and 14, respectively, were used to assess the probability of involvement of these loci in disease presentation. Common alleles transmitted from affected parent to affected child were determined where possible in the mutation-negative index cases. Allelic frequencies of these alleles were compared to findings in the normal population, but no predominant disease-associated allele could be identified. Co-segregation of a specific haplotype with the disease phenotype could also not be demonstrated in a large Afrikaner family. It is concluded that further studies are warranted to determine the genetic factor(s) underlying the autosomal dominant pattern of inheritance in molecularly uncharacterized cases showing clinical symptoms of an acute porphyria. Copyright 1998 Academic Press.

Allosteric Inhibition of Human Porphobilinogen Synthase*

PubMed Central

Lawrence, Sarah H.; Ramirez, Ursula D.; Selwood, Trevor; Stith, Linda; Jaffe, Eileen K.

2009-01-01

Porphobilinogen synthase (PBGS) catalyzes the first common step in tetrapyrrole (e.g. heme, chlorophyll) biosynthesis. Human PBGS exists as an equilibrium of high activity octamers, low activity hexamers, and alternate dimer configurations that dictate the stoichiometry and architecture of further assembly. It is posited that small molecules can be found that inhibit human PBGS activity by stabilizing the hexamer. Such molecules, if present in the environment, could potentiate disease states associated with reduced PBGS activity, such as lead poisoning and ALAD porphyria, the latter of which is associated with human PBGS variants whose quaternary structure equilibrium is shifted toward the hexamer (Jaffe, E. K., and Stith, L. (2007) Am. J. Hum. Genet. 80, 329–337). Hexamer-stabilizing inhibitors of human PBGS were identified using in silico prescreening (docking) of ∼111,000 structures to a hexamer-specific surface cavity of a human PBGS crystal structure. Seventy-seven compounds were evaluated in vitro; three provided 90–100% conversion of octamer to hexamer in a native PAGE mobility shift assay. Based on chemical purity, two (ML-3A9 and ML-3H2) were subjected to further evaluation of their effect on the quaternary structure equilibrium and enzymatic activity. Naturally occurring ALAD porphyria-associated human PBGS variants are shown to have an increased susceptibility to inhibition by both ML-3A9 and ML-3H2. ML-3H2 is a structural analog of amebicidal drugs, which have porphyria-like side effects. Data support the hypothesis that human PBGS hexamer stabilization may explain these side effects. The current work identifies allosteric ligands of human PBGS and, thus, identifies human PBGS as a medically relevant allosteric enzyme. PMID:19812033

Congenital erythropoietic porphyria in an African hedgehog (Atelerix albiventris).

PubMed

Wolff, Carlos; Corradini, Paulina; Cortés, Galaxia

2005-06-01

A 6-mo-old, male African hedgehog (Atelerix albiventris) presented with a history of pink urine and demonstrating pink-colored teeth and mild hepatomegaly on examination. Urinalysis revealed no physical, chemical, or cellular abnormalities other than a pink color and fluorescence under ultraviolet light (UV). Also under UV, intense fluorescence of teeth, feet, and spines was noted. Porphyria was suspected. Spectrophotometric evaluation of urine showed extremely elevated levels of copro- and uroporphyrins. Analysis of the urine by thin-layer chromatography showed an abnormal pattern of excreted porphyrin intermediates. Urine high-performance thin-layer chromatography showed that excreted porphyrins were 90-95% of the type-I isomeric form, suggestive of congenital erythropoietic porphyria.

Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C.

PubMed

Takata, Kazuhide; Shakado, Satoshi; Sakamoto, Keiko; Fukuda, Hiromi; Yamauchi, Ryo; Fukuda, Sho; Kunimoto, Hideo; Umeda, Kaoru; Tanaka, Takashi; Yokoyama, Keiji; Morihara, Daisuke; Takeyama, Yasuaki; Irie, Makoto; Sakisaka, Shotaro

2017-10-01

Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.

A new mutation within the porphobilinogen deaminase gene leading to a truncated protein as a cause of acute intermittent porphyria in an extended Indian family.

PubMed

Flachsová, E; Verma, I C; Ulbrichová, D; Saxena, R; Zeman, J; Saudek, V; Raman, C S; Martásek, P

2007-01-01

Based on Internet search, we were contacted by a 50-year-old man suffering from severe abdominal pain. Acute hepatic porphyria was considered from positive Watson-Schwartz test. He, not being a health professional, searched for centres with ability to do molecular diagnosis and for information about therapeutic possibilities. He asked his physician for haem-arginate (Normosang, Orphan Europe, Paris) treatment, arranged sending his blood to our laboratory and mediated genetic counselling for him and his family. Molecular analyses of the PBGD gene revealed a novel mutation in exon 15, the 973insG. Subsequently, genetic analysis was performed in 18 members of the proband's extensive family. In 12 members of the family, the same mutation was found. The mutation, which consisted of one nucleotide insertion, resulted in addition of four different amino acids leading to a protein that is prematurely truncated by the stop codon. The effect of this mutation was investigated by expression of the wildtype and mutated PBGD in a prokaryotic expression system. The mutation resulted in instability of the protein and loss of enzymatic function. The increasing access to a number of disease- and symptom-oriented web pages presents a new and unusual venue for gaining knowledge and enabling self-diagnosis and self-help. It is, therefore, important that diseaseoriented Internet pages for public use should be designed with clarity and accurate current knowledge based background.

Guide to drug porphyrogenicity prediction and drug prescription in the acute porphyrias

PubMed Central

Thunell, Stig; Pomp, Erik; Brun, Atle

2007-01-01

What is already known about this subject Many drug safety lists for acute porphyrias, largely based on anecdotal evidence, are put forward, but no methods or rationale for the risk estimates are given. Many unexplained discrepancies between the lists exist. What this study adds A standardized method for assessment of the risk that a certain drug may activate these diseases has been developed. It also allows risk assessments for drugs lacking porphyria related clinical experience. About one thousand therapeutic drugs have been classified with regard to porphyrogenicity by the proposed method, which is most valuable for the care of porphyria patients. Aims This paper addresses two common problems in the care of carriers of acute porphyria: the choice of safe drugs for pharmacotherapy and the strategy to apply when potentially unsafe drugs cannot be avoided. Methods and results A technique is presented for prediction of risk that a certain drug may activate the disease in a gene carrier for acute porphyria. It is based on a model explaining the clinical manifestations as a result of the acute overloading of a deficient enzyme within the hepatic heme biosynthetic chain. The capacity of the drug for induction of the rate-limiting enzyme in heme biosynthesis, e.g. housekeeping 5-aminolevulinate synthase (ALAS1), is assessed by critical appraisal of reports of the outcomes of clinical use of the drug, and by theoretical criteria. The assessment occurs within the frame of a flow-scheme employing variables of increasing specificity, i.e. endocrine properties of the drug, structure and metabolism pointing to affinity to cytochrome P450, hepatic load in therapeutic use, recognized affinity to major CYP species, capacity for CYP-induction or irreversible inhibition, and capacity to activate or modulate the transduction mechanisms of nuclear receptors affecting ALAS1-gene transcription. It is proposed that in the absence of a safer alternative, an urgently needed drug not should be withheld on the grounds of potential porphyrogenicity. After risk-benefit analysis it should be prescribed, but individualized preventive measures adapted to patient vulnerability may be needed. Conclusions About 1000 therapeutic drugs categorized with regard to porphyrogenicity by the technique proposed are presented on the internet (http://www.drugs-porphyria.org). PMID:17578481

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2010 CFR

2010-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2013 CFR

2013-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2011 CFR

2011-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2012 CFR

2012-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

38 CFR 3.813 - Interim benefits for disability or death due to chloracne or porphyria cutanea tarda.

Code of Federal Regulations, 2014 CFR

2014-07-01

... rates that dependency and indemnity compensation would be payable if the death were service-connected... disability or death due to chloracne or porphyria cutanea tarda. 3.813 Section 3.813 Pensions, Bonuses, and... Indemnity Compensation Special Benefits § 3.813 Interim benefits for disability or death due to chloracne or...

Characterization of variegate porphyria mutations using a minigene approach.

PubMed

Granata, Barbara Xoana; Baralle, Marco; De Conti, Laura; Parera, Victoria; Rossetti, Maria Victoria

2015-01-01

Porphyrias are a group of metabolic diseases that affect the skin and/or nervous system. In 2008, three unrelated patients were diagnosed with variegate porphyria at the CIPYP (Centro de Investigaciones sobre Porfirinas y Porfirias). Sequencing of the protoporphyrinogen oxidase gene, the gene altered in this type of porphyria, revealed three previously undescribed mutations: c.338+3insT, c.807G>A, and c.808-1G>C. As these mutations do not affect the protein sequence, we hypothesized that they might be splicing mutations. RT-PCRs performed on the patient's mRNAs showed normal mRNA or no amplification at all. This result indicated that the aberrant spliced transcript is possibly being degraded. In order to establish whether they were responsible or not for the patient's disease by causing aberrant splicing, we utilized a minigene approach. We found that the three mutations lead to exon skipping; therefore, the abnormal mRNAs are most likely degraded by a mechanism such as nonsense-mediated decay. In conclusion, these mutations are responsible for the disease because they alter the normal splicing pathway, thus providing a functional explanation for the appearance of disease and highlighting the use of minigene assays to complement transcript analysis.

An Audit of the Use of Gonadorelin Analogues to Prevent Recurrent Acute Symptoms in Patients with Acute Porphyria in the United Kingdom.

PubMed

Schulenburg-Brand, Danja; Gardiner, Tricia; Guppy, Simon; Rees, David C; Stein, Penelope; Barth, Julian; Felicity Stewart, M; Badminton, Michael

2017-01-01

Severe recurrent acute attacks of porphyria have traditionally been treated with either prophylactic human haemin or gonadorelin analogues (GnA) in females. Evidence on the most effective treatment for this patient subgroup is lacking. This audit surveyed the use of prophylactic GnA in the UK.Twenty female patients (who experienced between 2 and 45 acute attacks of porphyria requiring hospitalisation and treatment with human haemin prior to GnA prophylaxis) were included in the audit. Data was retrospectively collected based on patient history and case review.Twenty three treatment courses were given lasting a median period of 12 months. Monthly subcutaneous Goserelin was most commonly used. In three patients in whom timing with the menstrual cycle was not considered, an acute attack occurred after initiation of the first dose. The majority of patients experienced oestrogen deficiency symptoms during treatment. Fifty percent of the prescribed courses of GnA resulted in a degree of clinical benefit. This successfully treated group experienced between 3 and 20 acute attacks prior to and between 0 and 6 acute attacks during GnA treatment.The audit revealed large variation in practice in the United Kingdom regarding indication, duration of treatment, specific drug used and management of side effects. In view of the limited treatment options available for this cohort and the mixed outcome successes reported, we believe it is reasonable for porphyria specialists to continue offering GnA treatment to women with severe recurrent debilitating acute attacks of porphyria associated with the menstrual cycle, and we propose best practice guidelines to standardise management.

Herbicide-induced experimental variegate porphyria in mice: tissue porphyrinogen accumulation and response to porphyrogenic drugs.

PubMed

Krijt, J; Stranska, P; Maruna, P; Vokurka, M; Sanitrak, J

1997-01-01

Administration of oxadiazon or oxyfluorfen (1000 ppm in the diet) to male BALB/c mice for 9 days resulted in experimental porphyria, resembling the acute phase of human variegate porphyria. Urinary concentrations of 5-aminolevulinic acid and porphobilinogen reached 1500 and 3000 mumol/L, respectively. Both herbicides caused a decrease of protoporphyrinogen oxidase activity in liver and kidney. Brain protoporphyrinogen oxidase activity was not altered. Liver and kidney porphyrin content increased to 11 and 17 nmol/g, respectively (control mice, 2 nmol/g). Over 50% of liver and kidney porphyrins were in the reduced (porphyrinogen) form. Bile of oxadiazon-treated mice contained 700 nmol/mL of protoporphyrinogen (control mice, 15 nmol/mL). Porphyrin content of the trigeminal nerve increased from 1 nmol/g in control animals to 11 nmol/g in oxadiazon-treated animals, suggesting a possible contribution of peripheral nerve porphyrins to porphyric neuropathy. Mice treated with 125 ppm of oxadiazon in the diet for 9 days excreted moderately elevated levels of porphobilinogen in urine (control mice, less than 50 mumol/L; treated mice, 330 mumol/L). Administration of phenobarbital or phenytoin (single injections on days 7, 8, and 9) increased the urinary porphobilinogen concentration to 3500 mumol/L. This response to porphyrogenic drugs resembles the response observed in human acute porphyrias.

Acute porphyrias: clinical spectrum of hospitalized patients.

PubMed

Sheerani, Mughis; Urfy, Mian Zainulsajadeen; Hassan, Ali; Islam, Zunaira; Baig, Shahid

2007-11-01

To determine characteristics, clinical features and triggers of acute porphyria in hospitalized patients presenting to a tertiary care center in Pakistan. Case series. The Aga Khan University Hospital, Karachi, from 1988 to 2003. Case records of 26 patients hospitalized with diagnosis were identified through computerized hospital patients' data. The diagnosis of acute porphyria was based on pertinent clinical features and laboratory investigations after exclusion of other alternative diagnosis and patients previously diagnosed as porphyric. The data was analyzed through SPSS software version 11.0. Twelve patients (46.2%) were males. Mean age was 21 years. Most common manifestation were gastrointestinal (n=22; 88.5%) followed by neurological symptoms (n=14; 54%). Neurological manifestations included seizures (n=9; 34.6%) and neuropathy (n=6; 23%). One patient presented with depression and insomnia. Family history was positive in (n=8; 30.8%). Eighteen (69%) had history of previous attacks at their presentation to the hospital. Most common precipitating factor was 'eating outside' (n=18; 69%). Porphyrias are uncommon and cryptic group of diseases. This study shows a slightly different gender distribution, earlier onset of symptoms, higher number of neuropsychiatric symptoms (especially seizures), more distal neuropathies and different precipitant in the studied subset of patients than described previously in the western studies.

Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm.

PubMed

Luck, Margaux; Schmitt, Caroline; Talbi, Neila; Gouya, Laurent; Caradeuc, Cédric; Puy, Hervé; Bertho, Gildas; Pallet, Nicolas

2018-01-01

Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease. In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses. Urine 1 H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained. Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients. These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism.

Activation of the complement system in patients with porphyrias after irradiation in vivo.

PubMed Central

Lim, H W; Poh-Fitzpatrick, M B; Gigli, I

1984-01-01

Irradiation of the forearms of two patients with erythropoietic protoporphyria and one patient with porphyria cutanea tarda resulted in an in vivo activation of the complement system, as assessed by diminution of the hemolytic titers of the third component of complement by 23-57%, and of the fifth component of complement (C5) by 19-47%. Such treatment also generated chemotactic activity for human polymorphonuclear cells; the chemotactic activity was stable at 56 degrees C and antigenically related to human C5. On Sephadex G-75 chromatography the chemotactic activity eluted with an apparent molecular weight of 15,000. These in vivo results extend our previous in vitro observation of photoactivation of complement in sera from patients with erythropoietic protoporphyria and porphyria cutanea tarda, and suggest that the complement system may participate in the pathogenesis of cutaneous phototoxicity in these patients. PMID:6392339

Diagnosing the dead: the retrospective analysis of genetic diseases.

PubMed

Rushton, A R

2013-01-01

The suspected presence of hereditary disease in important historical and political figures has interested researchers for many decades. Whether Abraham Lincoln suffered from Marfan syndrome, if George III became 'mad' because he inherited variegate porphyria, and if the Romanov dynasty collapsed because the heir Alexei inherited haemophilia are important questions; physical illness can adversely affect the ability of leaders to function within the social and political realm of their day. This article will outline an approach to such a medical-historical analysis including assessment of hereditary predisposition, family history and the use of DNA technology to confirm or deny the clinical suspicions of the investigator.

Homozygous variegate porphyria presenting with developmental and language delay in childhood.

PubMed

Pinder, V A E; Holden, S T; Deshpande, C; Siddiqui, A; Mellerio, J E; Wraige, E; Powell, A M

2013-10-01

Variegate porphyria is an autosomal dominant disorder that usually presents with photosensitivity and acute neurological crises in adulthood. It is caused by heterozygous mutations in the protoporphyrinogen oxidase gene (PPOX). A rarer variant, homozygous variegate porphyria (HVP), presents in childhood with recurrent skin blisters and scarring. More variable features of HVP are short stature, brachydactyly, nystagmus, epilepsy, developmental delay and mental retardation. We describe a child who presented with nystagmus, developmental delay and ataxia, combined with a photosensitive eruption. Analysis of porphyrins in plasma, urine and stool supported a clinical diagnosis of HVP. DNA from the patient showed that he is compound heterozygous for two novel missense mutations in the PPOX coding region: c.169G>C (p.Gly57Arg) and c.1259C>G (Pro420Arg). Interestingly, cranial magnetic resonance imaging showed an absence of myelin, a feature not previously reported in HVP, which expands the differential diagnosis of childhood hypomyelinating leucoencephalopathies. © 2013 British Association of Dermatologists.

Uroporphyrin I Stimulation of Collagen Biosynthesis in Human Skin Fibroblasts

PubMed Central

Varigos, George; Schiltz, John R.; Bickers, David R.

1982-01-01

Porphyria cutanea tarda and erythropoietic porphyria are disorders of heme synthesis that originate in the liver and bone marrow, respectively. Each is characterized by increased accumulation of uroporphyrin, I, by cutaneous photosensitivity, and in some patients by indurated plaques and scarring that resemble scleroderma. These scleroderma-like lesions occur in light-exposed and light-protected body areas. In these studies we evaluated the role of uroporphyrin I and of light in evoking the scleroderma-like cutaneous changes. Normal human skin fibroblasts were exposed to uroporphyrin I and to 400 nm radiation and the effect of these agents on collagen accumulation by the cells was determined. Radioactive tracer studies showed that uroporphyrin I caused a specific increase in the accumulation of newly synthesized collagen by fibroblast monolayer cultures, as verified by [3H]hydroxyproline and collagenase digestion assays. Collagen accumulation was stimulated 1.5- to 2.7-fold by uroporphyrin I, whereas noncollagenous protein accumulation was unchanged. The increased collagen accumulation was time and uroporphyrin I-concentration-dependent, and occurred both in the presence or absence of ultraviolet light exposure. Further studies demonstrated that the increased accumulation was not the result of decreased rates of collagen degradation nor was it due to changes in cell population growth parameters (generation times and saturation densities). No changes in morphology of the treated cells occurred. These studies indicate that porphyrins possess previously undemonstrated biological effects that are independent of their photosensitizing properties. This novel dark effect of uroporphyrin I may account for the sclerodermatous lesions seen in the skin of patients with porphyria cutanea tarda and erythropoietic porphyria. PMID:7054234

Current Concepts in Dermatology

PubMed Central

Jackson, Robert

1963-01-01

Many systemic diseases have cutaneous manifestations. In some diseases skin involvement is the predominant factor (Behçet's syndrome, urticaria pigmentosa, discoid lupus erythematosus and pseudoxanthoma elasticum); in others the skin manifestations, when present, are an important part of the condition (sarcoidosis, systemic lupus erythematosus, hypersensitivity angiitis, porphyria). This report includes descriptions of and comments on these cutaneous manifestations. Erythema nodosum and erythema multiforme are reaction patterns of the skin and mucous membrane which may have many causes. The relationship between discoid and systemic lupus erythematosus is discussed. There is little doubt that these are variations of the same basic disease process, even though the prognoses are very different. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:14063940

May 2006 update in porphobilinogen deaminase gene polymorphisms and mutations causing acute intermittent porphyria: comparison with the situation in Slavic population.

PubMed

Hrdinka, M; Puy, H; Martasek, P

2006-01-01

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis caused by molecular defects in the porphobilinogen deaminase (PBGD) gene. This paper reviews published mutations, their types, and polymorphisms within the PBGD gene. To date, 301 different mutations and 21 polymorphisms have been identified in the PBGD gene in AIP patients and individuals from various countries and ethnic groups. During the search for mutations identified among Slavic AIP patients we found 65 such mutations and concluded that there is not a distinct predominance of certain mutations in Slavs.

An update of clinical management of acute intermittent porphyria

PubMed Central

Pischik, Elena; Kauppinen, Raili

2015-01-01

Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. PMID:26366103

Porphyria

MedlinePlus

... Process Research Training & Career Development Funded Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive ...

Studies in porphyria: functional evidence for a partial deficiency of ferrochelatase activity in mitogen-stimulated lymphocytes from patients with erythropoietic protoporphyria.

PubMed Central

Sassa, S; Zalar, G L; Poh-Fitzpatrick, M B; Anderson, K E; Kappas, A

1982-01-01

In this paper we show that the ferrochelatase defect in erythropoietic protoporphyria (EPP) can readily be identified in mitogen-stimulated lymphocytes since such cells from patients with EPP accumulate approximately twice as much protoporphyrin IX as cells from normal subjects when incubated with a porphyrin precursor, gamma-aminolevulinic acid (ALA). Treatment of cultures with ALA and with the iron chelator, CaMgEDTA significantly increased the level of protoporphyrin IX in mitogen-stimulated lymphocytes from normal subjects, while the same treatment failed to produce an increase in protoporphyrin IX in cell preparations from EPP patients. In contrast to the results with the chelator treatment, supplementation of the cultures with iron and ALA reduced the level of protoporphyrin IX in normal cells, but not in EPP cells. These findings are compatible with a partial deficiency of ferrochelatase in EPP lymphocytes. The gene defects of acute intermittent porphyria and hereditary coproporphyria have previously been identified using lymphocyte preparations from the gene carriers of these diseases. The present study demonstrates that EPP represents another form of human porphyria in which the gene defect of the disease can now be identified in lymphocyte preparations. PMID:6804493

A filter paper dry blood spot procedure for acute intermittent porphyria population screening by use of whole blood uroporphyrinogen-I-synthase assay.

PubMed

Johansson, L; Thunell, S; Wetterberg, L

1984-03-13

A filter paper dry blood spot procedure for the determination of whole blood uroporphyrinogen-I-synthase (UIS) activity is presented. The method is based on the concept of enzyme specific activity, the enzyme activity being related to the haemoglobin concentration of the assay sample. The diagnostic capacity with regard to the acute intermittent porphyria (AIP) gene carrier state is shown to be equivalent to that of a washed red cell reference method. On grounds of easy capillary blood sampling, uncomplicated and safe mail specimen transport and simple laboratory reception routines, the method is stated to be well adapted for use in AIP preadolescent population screening.

Porphyria

MedlinePlus

... numbness, tingling, paralysis, or cramping; vomiting; constipation; and personality changes or mental disorders. These symptoms come and go. Certain triggers can cause an attack, including some medicines, smoking, drinking alcohol, ...

Hematin and propranolol in acute intermittent porphyria. Full recovery from quadriplegic coma and respiratory failure.

PubMed

Brezis, M; Ghanem, J; Weiler-Ravell, D; Epstein, O; Morris, D

1979-01-01

The authors present a case of acute intermittent porphyria (AIP) in an almost fatal relapse with quadriplegia, bulbar paralysis and coma. Intravenous hematin produced an immediate arousal from coma and allowed a gradual resumption of bulbar and autonomic functions. Persistent tachycardia and hypertension necessitated huge doses of intravenous propranolol. Both hematin and propranolol administrations were followed by a remarkable decrease in urinary amino-levulinic acid and porphobilinogen excretion. Nevertheless, after the acute stage, the patient was left with a severe generalized muscle wasting. After 7 months of intensive physical therapy, complete recovery of all neuromuscular functions was achieved. The modern aspects of the management of AIP are presented; the efficacy and the limits of hematin and propranolol therapy are discussed.

Porphyrins - urine test

MedlinePlus

Urine uroporphyrin; Urine coproporphyrin; Porphyria - uroporphyrin ... After you provide a urine sample, it is tested in the lab. This is called a random urine sample. If needed, your health care provider ...

Co-trimoxazole

MedlinePlus

... cannot digest the nutrients needed for good health); human immunodeficiency virus (HIV) infection; porphyria (an inherited blood disease that may cause skin or nervous system problems); thyroid disease; or glucose-6-phosphate dehydrogenase ( ...

Griseofulvin

MedlinePlus

... ever had liver disease, porphyria, lupus, or a history of alcohol abuse.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking griseofulvin, call ...

Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.

PubMed Central

Fujita, H; Sassa, S; Toback, A C; Kappas, A

1987-01-01

Hepatoerythropoietic porphyria (HEP) is due to a marked deficiency of uroporphyrinogen (URO) decarboxylase, a cytosolic enzyme in the heme biosynthetic pathway. Using a radioimmunoassay method, we determined the concentration of URO decarboxylase protein in erythrocytes from a patient with mild HEP and found that the enzyme protein concentration had markedly decreased to less than 7% of the normal controls. This finding, however, was in contrast to the enzyme activity in the patient's erythrocytes, which was 16% of normal control levels and different from previously reported HEP cases in that erythrocytes in our patient contained disproportionately elevated URO decarboxylase activity in comparison to its immunoreactive material. Our findings suggests the possibility of a mutant isozyme in this patient that is not immunoreactive with an antibody raised against the normal enzyme. PMID:3571497

Congenital Erythropoietic Porphyria (CEP)

MedlinePlus

... can be severe and such patients require periodic transformations to maintain sufficient red blood cells. In severely ... DAY FOR PATIENTS! date: Dec 9, 2017 PATIENT EDUCATION AND SUPPORT MEETING - ATLANTA » More upcoming events Athi ...

Porphyria Cutanea Tarda and Agent Orange

MedlinePlus

... of Medicine) of the National Academy of Sciences, Engineering, and Medicine concluded in its 1994 report on " ... VA Plans, Budget, & Performance VA Claims Representation RESOURCES Careers at VA Employment Center Returning Service Members Vocational ...

Meprobamate

MedlinePlus

... have ever had kidney or liver disease, a history of alcohol or drug abuse, porphyria, or epilepsy.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking meprobamate, call ...

FitzPatrick Lecture: King George III and the porphyria myth - causes, consequences and re-evaluation of his mental illness with computer diagnostics.

PubMed

Peters, Timothy

2015-04-01

Recent studies have shown that the claim that King George III suffered from acute porphyria is seriously at fault. This article explores some of the causes of this misdiagnosis and the consequences of the misleading claims, also reporting on the nature of the king's recurrent mental illness according to computer diagnostics. In addition, techniques of cognitive archaeology are used to investigate the nature of the king's final decade of mental illness, which resulted in the appointment of the Prince of Wales as Prince Regent. The results of this analysis confirm that the king suffered from bipolar disorder type I, with a final decade of dementia, due, in part, to the neurotoxicity of his recurrent episodes of acute mania. © 2015 Royal College of Physicians.

The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.

PubMed Central

Stine, O C; Smith, K D

1990-01-01

The effects of mutation, migration, random drift, and selection on the change in frequency of the alleles associated with Huntington disease, porphyria variegata, and lipoid proteinosis have been assessed in the Afrikaner population of South Africa. Although admixture cannot be completely discounted, it was possible to exclude migration and new mutation as major sources of changes in the frequency of these alleles by limiting analyses to pedigrees descendant from founding families. Calculations which overestimated the possible effect of random drift demonstrated that drift did not account for the observed changes in gene frequencies. Therefore these changes must have been caused by natural selection, and a coefficient of selection was estimated for each trait. For the rare, dominant, deleterious allele associated with Huntington disease, the coefficient of selection was estimated to be .34, indicating that this allele has a selective disadvantage, contrary to some recent studies. For the presumed dominant and probably deleterious allele associated with porphyria variegata, the coefficient of selection lies between .07 and .02. The coefficient of selection for the rare, clinically recessive allele associated with lipoid proteinosis was estimated to be .07. Calculations based on a model system indicate that the observed decrease in allele frequency cannot be explained solely on the basis of selection against the homozygote. Thus, this may be an example of a pleiotropic gene which has a dominant effect in terms of selection even though its known clinical effect is recessive. PMID:2137963

The estimation of selection coefficients in Afrikaners: Huntington disease, porphyria variegata, and lipoid proteinosis.

PubMed

Stine, O C; Smith, K D

1990-03-01

The effects of mutation, migration, random drift, and selection on the change in frequency of the alleles associated with Huntington disease, porphyria variegata, and lipoid proteinosis have been assessed in the Afrikaner population of South Africa. Although admixture cannot be completely discounted, it was possible to exclude migration and new mutation as major sources of changes in the frequency of these alleles by limiting analyses to pedigrees descendant from founding families. Calculations which overestimated the possible effect of random drift demonstrated that drift did not account for the observed changes in gene frequencies. Therefore these changes must have been caused by natural selection, and a coefficient of selection was estimated for each trait. For the rare, dominant, deleterious allele associated with Huntington disease, the coefficient of selection was estimated to be .34, indicating that this allele has a selective disadvantage, contrary to some recent studies. For the presumed dominant and probably deleterious allele associated with porphyria variegata, the coefficient of selection lies between .07 and .02. The coefficient of selection for the rare, clinically recessive allele associated with lipoid proteinosis was estimated to be .07. Calculations based on a model system indicate that the observed decrease in allele frequency cannot be explained solely on the basis of selection against the homozygote. Thus, this may be an example of a pleiotropic gene which has a dominant effect in terms of selection even though its known clinical effect is recessive.

Computer-based diagnosis of illness in historical persons.

PubMed

Peters, T J

2013-01-01

Retrospective diagnosis of illness in historical figures is a popular but somewhat unreliable pastime due to the lack of detailed information and reliable reports about clinical features and disease progression. Modern computer-based diagnostic programmes have been used to supplement historical documents and accounts, offering new and more objective approaches to the retrospective investigations of the medical conditions of historical persons. In the case of King George III, modern technology has been used to strengthen the findings of previous reports rejecting the popular diagnosis of variegate porphyria in the King, his grandson Augustus d'Esté and his antecedent King James VI and I. Alternative diagnoses based on these programmes are indicated. The Operational Criteria in Studies of Psychotic Illness (OPCRIT) programme and the Young mania scale have been applied to the features described for George III and suggest a diagnosis of bipolar disorder. The neuro-diagnostic programme SimulConsult was applied to Augustus d'Esté and suggests a diagnosis of neuromyelitis optica rather than acute porphyria with secondarily multiple sclerosis, as proposed by others. James VI and I's complex medical history and the clinical features of his behavioural traits were also subjected to SimulConsult analysis; acute porphyria was rejected and the unexpected diagnosis of attenuated (mild) Lesch-Nyhan disease offered. A brief review of these approaches along with full reference listings to the methodology including validation are provided. Textual analysis of the written and verbal outputs of historical figures indicate possible future developments in the diagnosis of medical disorders in historical figures.

Health hazard evaluation report HETA-83-297-1846, truck terminals, St. Louis, Missouri

DOE Office of Scientific and Technical Information (OSTI.GOV)

McConnell, R.S.; Anderson, K.E.

1987-11-01

An evaluation was made of possible exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at trucking terminals in St. Louis, Missouri. A self-selected group of workers participated in a medical survey. A significant association was noted between symptoms of numbness in hands and feet, pins and needles in the extremities, insomnia and feelings of depression, and possible exposure to TCDD. One case of porphyria cutanea tarda and one of dermatofibrosarcoma were reported. The patient with porphyria cutanea tarda later developed a pelvic angiosarcoma. Environmental samples revealed a dioxin concentration of about 18.7 parts per billion on the rafters inside a terminal. Dioxin was presentmore » in two surface soil samples taken near an entrance gate. The authors conclude that no definite association between TCDD exposure and symptoms or medical problems can be established. The authors recommended that measures be taken to control or eliminate possible exposures at the terminals.« less

Feline congenital erythropoietic porphyria associated with severe anemia and renal disease. Clinical, morphologic, and biochemical studies.

PubMed Central

Giddens, W. E.; Labbe, R. F.; Swango, L. J.; Padgett, G. A.

1975-01-01

A feline erythropoietic porphyria was studied in an affected female Siamese cat and 2 male offspring. The principal elevated porphyrins were Type I isomers of uroporphyrin and coproporphyrin; the porphyrin precursors, porphobilinogen and sigma-aminolevulinic acid, were also detected. Porphyrins were present in the blood and in all the viscera, teeth, bones, and excreta. There was severe macrocytic hypochromic anemia, hepatomegaly, splenomegaly, and uremia associated with a renal disease characterized by mesangial hypercellularity and proliferation (resulting in narrowing of glomerular capillaries) and ischemic tubular injury. There was thickening of tubular basement membranes and tubular epithelial lipidosis, degeneration, and necrosis. Electron microscopic studies of bone marrow and kidney revealed the presence of membrane-enclosed lamellar bodies 150 to 1000 nm in diameter in cytoplasmic and extracellular locations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:1231563

Assessment of Intra-subject Variability in the Bioavailability of Chlorpromazine Hydrochloride

ClinicalTrials.gov

2017-10-12

Anti-Psychotic; Management of Manifestations of Psychotic Disorders; Treatment of Schizophrenia; Control Nausea and Vomiting; Relief of Restlessness and Apprehension Before Surgery; Acute Intermittent Porphyria; Adjunct in the Treatment of Tetanus; Control Manifestations of the Manic Type of Mani-depressive Illness; Relief of Intractable Hiccups

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

21 CFR 862.1060 - Delta-aminolevulinic acid test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... poisoning and certain porphyrias (diseases affecting the liver, gastrointestinal, and nervous systems that... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Delta-aminolevulinic acid test system. 862.1060... Systems § 862.1060 Delta-aminolevulinic acid test system. (a) Identification. A delta-aminolevulinic acid...

Studying disorders of vertebrate iron and heme metabolism using zebrafish

PubMed Central

van der Vorm, Lisa N.; Paw, Barry H.

2017-01-01

Iron is a crucial component of heme- and iron-sulfur clusters, involved in vital cellular functions such as oxygen transport, DNA synthesis, and respiration. Both excess and insufficient levels of iron and heme-precursors cause human disease, such as iron-deficiency anemia, hemochromatosis, and porphyrias. Hence, their levels must be tightly regulated, requiring a complex network of transporters and feedback mechanisms. The use of zebrafish to study these pathways and the underlying genetics offers many advantages, among others their optical transparency, ex-vivo development and high genetic and physiological conservations. This chapter first reviews well-established methods, such as large-scale mutagenesis screens that have led to the initial identification of a series of iron and heme transporters and the generation of a variety of mutant lines. Other widely used techniques are based on injection of RNA, including complementary morpholino knockdown and gene overexpression. In addition, we highlight several recently developed approaches, most notably endonuclease-based gene knockouts such as TALENs or the CRISPR/Cas9 system that have been used to study how loss of function can induce human disease phenocopies in zebrafish. Rescue by chemical complementation with iron-based compounds or small molecules can subsequently be used to confirm causality of the genetic defect for the observed phenotype. All together, zebrafish have proven to be – and will continue to serve as an ideal model to advance our understanding of the pathogenesis of human iron and heme-related diseases and to develop novel therapies to treat these conditions. PMID:28129844

Pearls and pitfalls in the horror cinema.

PubMed

Pascuzzi, R M

1998-01-01

Observations on the neurologic signs and symptoms of Count Dracula, Wolfman, and Frankenstein's Monster are presented as viewed by a specialist in neuromuscular disease. Key clinical features of these horror movie figures illustrate a variety of pearls in the diagnosis of a variety of neurologic disorders, including porphyria, lead poisoning, osteosclerotic myeloma, and myasthenia gravis.

Effect of the protoporphyrinogen oxidase-inhibiting herbicide fomesafen on liver uroporphyrin and heptacarboxylic porphyrin in two mouse strains.

PubMed

Krijt, J; Vokurka, M; Sanitrak, J; Janousek, V; van Holsteijn, I; Blaauboer, B J

1994-07-01

The effect of the protoporphyrinogen oxidase-inhibiting herbicide fomesafen on liver porphyrin accumulation was studied in long-term high-dose experiments. Fomesafen caused liver accumulation of uroporphyrin and heptacarboxylic porphyrin when fed at 0.25% in the diet to male ICR mice for 5 months (fomesafen-treated mice: 52 nmol uroporphyrin, 21 nmol heptacarboxylic porphyrin/g liver; control mice: traces of uroporphyrin, heptacarboxylic porphyrin not detected). Uroporphyrinogen decarboxylase activity was depressed to about 25% of control values. Iron treatment accelerated the development of this porphyria cutanea tarda-like experimental porphyria both in ICR and C57B1/6J mice. In contrast to other uroporphyrinogen decarboxylase inhibitors, fomesafen treatment did not increase the cytochrome P450IA-related activities and the amount of P450IA2 protein was shown to be significantly decreased by Western immunoblotting. Thus, fomesafen is a unique chemical that inhibits both the oxidation of protoporphyrinogen as well as the conversion of uroporphyrinogen to coproporphyrinogen. However, the accumulation of highly carboxylated porphyrins is evident only after prolonged treatment with high doses of the herbicide.

Comprehensive analysis of the tryptophan metabolome in urine of patients with acute intermittent porphyria.

PubMed

Gomez-Gomez, Alex; Marcos, Josep; Aguilera, Paula; To-Figueras, Jordi; Pozo, Oscar J

2017-08-15

Acute intermittent porphyria (AIP) is a rare metabolic disorder due to a deficiency of porphobilinogen deaminase, the third enzyme of the heme biosynthetic pathway. This low enzymatic activity may predispose to the appearance of acute neurological attacks. Seminal studies suggested that AIP was associated with changes in tryptophan homeostasis with inconclusive results. Therefore, the aim of this study was to analyze the urinary metabolome of AIP patients focusing on tryptophan metabolism using state-of-the-art technology. This was a case-control study including a group of 25 AIP patients with active biochemical disease and increased excretion of heme-precursors and 25 healthy controls. Tryptophan and related compounds and metabolites including: large neutral amino acids (LNAAs), serotonin, kynurenine, kynurenic acid and anthranilic acid were quantified in urine by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Twenty-nine biological markers (including metabolic ratios and absolute concentrations) were compared between patients and controls. Significant differences were found in the tryptophan-kynurenine metabolic pathway. Compared to controls, AIP patients showed: (a) increased urinary excretion of kynurenine and anthranilic acid (P<0.005); (b): elevation of the kynurenine/tryptophan ratio (P<0.001) and (c): decrease of the kynurenic acid/kynurenine ratio (P=0.001). In contrast, no differences were found in the serotonin metabolic pathway independently of the markers and ratios used. The results of the study demonstrate that there is an imbalance in the kynurenine metabolic pathway in AIP patients, with an increase of the kynurenine/tryptophan ratio in urine and a reduction of the kynurenic acid/kynurenine ratio. The modified ratios suggest induction of indoleamine 2,3-deoxygenase and decreased activity of kynurenine aminotransferase in the liver. The results confirm that LC-MS/MS is useful for the characterization of the urinary metabolome of hepatic porphyrias. Copyright © 2017. Published by Elsevier B.V.

Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice.

PubMed

Iwadate, Reiko; Satoh, Yoko; Watanabe, Yukino; Kawai, Hiroshi; Kudo, Naomi; Kawashima, Yoichi; Mashino, Tadahiko; Mitsumoto, Atsushi

2012-07-01

It has been demonstrated that the function of mammalian clock gene transcripts is controlled by the binding of heme in vitro. To examine the effects of heme on biological rhythms in vivo, we measured locomotor activity (LA) and core body temperature (T(b)) in a mouse model of porphyria with impaired heme biosynthesis by feeding mice a griseofulvin (GF)-containing diet. Mice fed with a 2.0% GF-containing diet (GF2.0) transiently exhibited phase advance or phase advance-like phenomenon by 1-3 h in terms of the biological rhythms of T(b) or LA, respectively (both, P < 0.05) while mice were kept under conditions of a light/dark cycle (12 h:12 h). We also observed a transient, ~0.3 h shortening of the period of circadian T(b) rhythms in mice kept under conditions of constant darkness (P < 0.01). Interestingly, the observed duration of abnormal circadian rhythms in GF2.0 mice lasted between 1 and 3 wk after the onset of GF ingestion; this finding correlated well with the extent of impairment of heme biosynthesis. When we examined the effects of therapeutic agents for acute porphyria, heme, and hypertonic glucose on the pathological status of GF2.0 mice, it was found that the intraperitoneal administration of heme (10 mg·kg(-1)·day(-1)) or glucose (9 g·kg(-1)·day(-1)) for 7 days partially reversed (50%) increases in urinary δ-aminolevulinic acids levels associated with acute porphyria. Treatment with heme, but not with glucose, suppressed the phase advance (-like phenomenon) in the diurnal rhythms (P < 0.05) and restored the decrease of heme (P < 0.01) in GF2.0 mice. These results suggest that impairments of heme biosynthesis, in particular a decrease in heme, may affect phase and period of circadian rhythms in animals.

Genetic background effects of keratin 8 and 18 in a DDC-induced hepatotoxicity and Mallory-Denk body formation mouse model.

PubMed

Haybaeck, Johannes; Stumptner, Cornelia; Thueringer, Andrea; Kolbe, Thomas; Magin, Thomas M; Hesse, Michael; Fickert, Peter; Tsybrovskyy, Oleksiy; Müller, Heimo; Trauner, Michael; Zatloukal, Kurt; Denk, Helmut

2012-06-01

Keratin 8 (K8) and keratin 18 (K18) form the major hepatocyte cytoskeleton. We investigated the impact of genetic loss of either K8 or K18 on liver homeostasis under toxic stress with the hypothesis that K8 and K18 exert different functions. krt8⁻/⁻ and krt18⁻/⁻ mice crossed into the same 129-ola genetic background were treated by acute and chronic administration of 3,5-diethoxy-carbonyl-1,4-dihydrocollidine (DDC). In acutely DDC-intoxicated mice, macrovesicular steatosis was more pronounced in krt8⁻/⁻ and krt18⁻/⁻ compared with wild-type (wt) animals. Mallory-Denk bodies (MDBs) appeared in krt18⁻/⁻ mice already at an early stage of intoxication in contrast to krt8⁻/⁻ mice that did not display MDB formation when fed with DDC. Keratin-deficient mice displayed significantly lower numbers of apoptotic hepatocytes than wt animals. krt8⁻/⁻, krt18⁻/⁻ and control mice displayed comparable cell proliferation rates. Chronically DDC-intoxicated krt18⁻/⁻ and wt mice showed a similarly increased degree of steatohepatitis with hepatocyte ballooning and MDB formation. In krt8⁻/⁻ mice, steatosis was less, ballooning, and MDBs were absent. krt18⁻/⁻ mice developed MDBs whereas krt8⁻/⁻ mice on the same genetic background did not, highlighting the significance of different structural properties of keratins. They are independent of the genetic background as an intrinsic factor. By contrast, toxicity effects may depend on the genetic background. krt8⁻/⁻ and krt18⁻/⁻ mice on the same genetic background show similar sensitivity to DDC intoxication and almost resemble wt animals regarding survival, degree of porphyria, liver-to-body weight ratio, serum bilirubin and liver enzyme levels. This stands in contrast to previous work where krt8⁻/⁻ and krt18⁻/⁻ mice on different genetic backgrounds were investigated.

Spectral design flexibility of LED brings better life

NASA Astrophysics Data System (ADS)

Ou, Haiyan; Corell, Dennis; Ou, Yiyu; Poulsen, Peter B.; Dam-Hansen, Carsten; Petersen, Paul-Michael

2012-03-01

Light-emitting diodes (LEDs) are penetrating into the huge market of general lighting because they are energy saving and environmentally friendly. The big advantage of LED light sources, compared to traditional incandescent lamps and fluorescent light tubes, is the flexible spectral design to make white light using different color mixing schemes. The spectral design flexibility of white LED light sources will promote them for novel applications to improve the life quality of human beings. As an initial exploration to make use of the spectral design flexibility, we present an example: 'no blue' white LED light source for sufferers of disease Porphyria. An LED light source prototype, made of high brightness commercial LEDs applying an optical filter, was tested by a patient suffering from Porphyria. Preliminary results have shown that the sufferer could withstand the light source for much longer time than the standard light source. At last future perspectives on spectral design flexibility of LED light sources improving human being's life will be discussed, with focus on the light and health. The good health is ensured by the spectrum optimized so that vital hormones (melatonin and serotonin) are produced during times when they support human daily rhythm.

Successful cord blood stem cell transplantation for congenital erythropoietic porphyria (Gunther's disease).

PubMed

Zix-Kieffer, I; Langer, B; Eyer, D; Acar, G; Racadot, E; Schlaeder, G; Oberlin, F; Lutz, P

1996-07-01

Congenital erythropoietic porphyria (Gunther's disease, GD) is a rare autosomal recessive disease. It results from the deficiency of uroporphyrinogen III synthase, the fourth enzyme on the metabolic pathway of heme synthesis. GD leads to severe scarring of the face and hands as a result of photosensitivity and fragility of the skin due to uroporphyrin I and coproporphyrin I accumulation. It also causes erythrocyte fragility leading to haemolytic anaemia. The other clinical features include hirsutism, red discolouration of teeth, finger-nails and urine and stunted growth. The outcome is poor, and the disfiguring nature of GD may partly explain the legend of the werewolf. No curative treatment was known until 1991, when the first case of BMT in GD was reported. The clinical and biological outcome after transplantation was encouraging, with an important regression of the symptoms of the disease, but the child died of CMV-infection 11 months after BMT. We report the second case of GD treated successfully by stem cell transplantation using umbilical cord blood from an HLA-identical brother in a 4-year-old girl suffering from severe GD. Our patient is very well 10 months after transplantation. We confirm that stem cell transplantation is curative for GD.

A case of teriparatide-induced severe hypophosphatemia and hypercalcemia.

PubMed

Hajime, Maiko; Okada, Yosuke; Mori, Hiroko; Tanaka, Yoshiya

2014-09-01

PTH (teriparatide) is used in the treatment of osteoporosis, and can sometimes cause transient hypercalcemia, but to date there have been no reports of persistent hypercalcemia and hypophosphatemia resulting from its use. We describe a case with marked hypophosphatemia and hypercalcemia associated with the use of teriparatide. The patient was a 49-year-old woman who was followed up for acute intermittent porphyria and glucocorticoid-induced osteoporosis (following administration of prednisolone at 22.5 mg/day), and presented with unexplained fracture of the left tibia, for which treatment with teriparatide at 20 μg/day was started. Two weeks after treatment with teriparatide, the patient developed hypophosphatemia, hypercalcemia, hyperalkaline phosphatasemia, low TmP/GFR, FEca, BAP, and urinary NT×, with low intact PTH. These changes were considered to be related to teriparatide. Cessation of teriparatide treatment resulted in normalization of all parameters at 10 weeks (serum P 3.6 mg/dl, corrected Ca 8.8 mg/dl, ALP 273 IU/l, intact PTH 63 pg/ml). The observed abnormalities were considered to be in part related to acute intermittent porphyria, which is known to delay hepatic teriparatide clearance, with subsequent delay of PTH action despite its intermittent use, resulting in hypercalcemia and hypophosphatemia.

Genetic variation of iron-induced uroporphyria in mice.

PubMed Central

Smith, A G; Francis, J E

1993-01-01

Iron overload causes inhibition of hepatic uroporphyrinogen decarboxylase (UROD) and uroporphyria in C57BL/10ScSn but not DBA/2 mice [Smith, Cabral, Carthew, Francis and Manson (1989) Int. J. Cancer 43, 492-496]. We have investigated the induction of uroporphyria in 12 inbred strains of mice 25 weeks after iron treatment (600 mg/kg) to determine if there was any correlation with the Ah locus. Under these conditions, inhibition of UROD occurred to varying degrees in Ahd mice (SWR and AKR) as well as nominally Ahb-1 (C57BL/6J, C57BL/10ScSn and C57BL/10-cc) and Ahb-2 strains (BALB/c and C3H/HeJ). Five other Ahb or Ahd strains (C57BL/Ks, A/J, CBA/J, LP and DBA/2) were unaffected. Thus there appeared to be no correlation with the Ah phenotype and this illustrated that some other variable inherited factors are involved. Comparisons between another susceptible strain, A2G, and the congenic A2G-hr/+strain (carrying the recessive hr gene) showed a modulating influence associated with the hr locus. In contrast with individual mice of inbred strains, which showed consistent responses to iron, those of the outbred MF1 strain showed a spectrum of sensitivities as might be expected for a heterogeneic stock. The rate of porphyria development was accelerated by administration of 5-aminolaevulinic acid (5-ALA) in the drinking water, but this did not overcome strain differences. Among four strains the order of susceptibility was SWR > C57BL/10ScSn > C57B1/6J > DBA/2 (the last strain was completely resistant). With degrees of iron loading greater than 600 mg of Fe/kg (1200-1800 mg of Fe/kg) C57BL/10ScSn mice (after 20 weeks) and SWR mice (after 5 weeks which included 4 weeks of 5-ALA treatment) had less inhibition of UROD and a lower uroporphyric response, showing that there was an optimum level of liver iron concentration. Studies on selected microsomal enzyme activities associated with cytochrome P-450 showed no correlation with the propensities of strains to develop porphyria. These activities included the NADPH-dependent oxidation of uroporphyrinogen I to uroporphyrin I. PMID:8471047

[The emphases and basic procedures of genetic counseling in psychotherapeutic model].

PubMed

Zhang, Yuan-Zhi; Zhong, Nanbert

2006-11-01

The emphases and basic procedures of genetic counseling are all different with those in old models. In the psychotherapeutic model, genetic counseling will not only focus on counselees' genetic disorders and birth defects, but also their psychological problems. "Client-centered therapy" termed by Carl Rogers plays an important role in genetic counseling process. The basic procedures of psychotherapeutic model of genetic counseling include 7 steps: initial contact, introduction, agendas, inquiry of family history, presenting information, closing the session and follow-up.

Photosensitive disorders in HIV

PubMed Central

2017-01-01

Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible. PMID:29568622

Photosensitive disorders in HIV.

PubMed

Koch, Karen

2017-01-01

Photosensitive disorders are common, affecting up to 5% of HIV-positive patients. HIV itself induces photosensitivity but photoaggravated drug reactions, porphyria cutanea tarda and nutritional disorders such as pellagra are also more common in patients with HIV. In South Africa, actinic lichenoid leukomelanoderma of HIV is a unique photosensitive disorder which is associated with advanced HIV. It is important to be able to recognise these conditions and withdraw photosensitising medications wherever possible.

Soren Kierkegaard (1813-55): a bicentennial pathographical review.

PubMed

Schioldann, Johan; Søgaard, Ib

2013-12-01

Researchers in the fields of psychology, psychiatry, medicine and theology have made exhaustive efforts to shed light on the elusive biography/pathography of the great Danish philosopher Søren Kierkegaard (1813-55). This 'bicentennial' article reviews his main pathographical diagnoses of, respectively, possible manic-depressive [bipolar] disease, epilepsy, complex partial seizure disorder, Landry-Guillain-Barré's acute ascending paralysis, acute intermittent porphyria with possible psychiatric manifestations, and syphilidophobia.

Learning Genetics with Paper Pets

ERIC Educational Resources Information Center

Finnerty, Valerie Raunig

2006-01-01

By the end of the eighth grade, students are expected to have a basic understanding of the mechanism of basic genetic inheritance. However, these concepts can be difficult to teach. In this article, the author introduces a new learning tool that will help facilitate student learning and enthusiasm to the basic concepts of genetic inheritance. This…

Insulin resistance in porphyria cutanea tarda.

PubMed

Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

1989-06-01

It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

PubMed

Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

2015-11-01

Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS.

N-Alkylprotoporphyrin Formation and Hepatic Porphyria in Dogs After Administration of a New Antiepileptic Drug Candidate: Mechanism and Species Specificity

PubMed Central

Nicolas, Jean-Marie; Chanteux, Hugues; Mancel, Valérie; Dubin, Guy-Marie; Gerin, Brigitte; Staelens, Ludovicus; Depelchin, Olympe; Kervyn, Sophie

2014-01-01

A new antiepileptic synaptic vesicle 2a (SV2a) ligand drug candidate was tested in 4-week oral toxicity studies in rat and dog. Brown pigment inclusions were found in the liver of high-dose dogs. The morphology of the deposits and the accompanying liver changes (increased plasma liver enzymes, increased total hepatic porphyrin level, decreased liver ferrochelatase activity, combined induction, and inactivation of cytochrome P-450 CYP2B11) suggested disruption of the heme biosynthetic cascade. None of these changes was seen in rat although this species was exposed to higher parent drug levels. Toxicokinetic analysis and in vitro metabolism assays in hepatocytes showed that dog is more prone to oxidize the drug candidate than rat. Mass spectrometry analysis of liver samples from treated dogs revealed an N-alkylprotoporphyrin adduct. The elucidation of its chemical structure suggested that the drug transforms into a reactive metabolite which is structurally related to a known reference porphyrogenic agent allylisopropylacetamide. That particular metabolite, primarily produced in dog but neither in rat nor in human, has the potential to alkylate the prosthetic heme of CYP. Overall, the data suggested that the drug candidate should not be porphyrogenic in human. This case study further exemplifies the species variability in the susceptibility to drug-induced porphyria. PMID:24973095

Genetic and Environmental Influences on Behavior: Capturing All the Interplay

ERIC Educational Resources Information Center

Johnson, Wendy

2007-01-01

Basic quantitative genetic models of human behavioral variation have made clear that individual differences in behavior cannot be understood without acknowledging the importance of genetic influences. Yet these basic models estimate average, population-level genetic and environmental influences, obscuring differences that might exist within the…

It's Not Your Grandmother's Genetics Anymore!

ERIC Educational Resources Information Center

Smith, Mike U.

2014-01-01

Genetics is perhaps the most rapidly growing field of science today. Recent findings such as those of the Human Genome Project have led to new understandings of basic genetic phenomena and even to increased confusion about some basic genetic ideas, such as the nature of the gene. These developments directly influence how we should teach genetics.…

Contradictory genetic make-up of Dutch harbour porpoises: Response to van der Plas-Duivesteijn et al.

NASA Astrophysics Data System (ADS)

Kopps, Anna M.; Palsbøll, Per J.

2016-02-01

The assessment of the status of endangered species or populations typically draw generously on the plethora of population genetic software available to detect population genetic structuring. However, despite the many available analytical approaches, population genetic inference methods [of neutral genetic variation] essentially capture three basic processes; migration, random genetic drift and mutation. Consequently, different analytical approaches essentially capture the same basic process, and should yield consistent results.

X-chromosomal inactivation directly influences the phenotypic manifestation of X-linked protoporphyria

PubMed Central

Brancaleoni, V.; Balwani, M.; Granata, F.; Graziadei, G.; Missineo, P.; Fiorentino, V.; Fustinoni, S.; Cappellini, M.D.; Naik, H.; Desnick, R.J.; Di Pierro, E.

2015-01-01

X-linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain-of-function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X-linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X-chromsomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc-finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X-chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild-type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin-containing peripheral blood fluorocytes. When the wild-type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP. PMID:25615817

[Hereditary haemochromatosis].

PubMed

Bismuth, Michael; Aguilar-Martinez, Patricia; Michel, Henri

2003-11-08

EPIDEMIOLOGY ADN PHYSIOPATHOLOGY: Hereditary haemochromatosis is the most common genetic disease in France. Its frequency is on average 1 out of 300 French individuals. It is due to excessive dietary iron absorption, leading to accumulation of iron in the body. Mutations of the HFE1 gene are responsible for the majority of the case of haemochromatosis. FROM A CLINICAL POINT OF VIEW: The first clinical manifestations (weakness, sexual dysfunction, arthralgia, cardiac symptoms, dyspnoea on effort) can occur after the age of 30 years in men and 35 years in women (protected for longer by menstruation, pregnancy and delivery). In the absence of diagnosis, severe complications can develop during the 5th decade: nervous breakdown, arthropathy, heart failure, diabetes mellitus, cirrhosis with risk of progression towards carcinoma, responsible for handicaps and premature death. DIAGNOSTIC ELEMENTS: The diagnosis is evoked in the case of an increase in transferrine saturation (>45%), associated or not with excessive ferritin plasma levels. It is confirmed by the genetic test, showing homozygotes for the C282Y mutation or compound heterozygotes for the C282Y and H63D mutations on the HFE1 gene. RMI quantifies hepatic iron loading and generally avoids the need for a liver biopsy. The differential diagnosis must exclude secondary iron overload due to chronic transfusions in congenital or acquired blood diseases, a polymetabolic syndrome, chronic viral or alcoholic hepatic diseases and porphyria cutanea tarda. EFFICIENT TREATMENT: Today, haemochromatosis is still treated by phlebotomy. This consists in withdrawing 400 to 500ml of blood every week at the initial depletion stage and subsequently a maintenance therapy in order to maintain ferritin levels below 50 ng/ml. Paradoxically and through ignorance, hereditary haemochromatosis remains a serious disease, although its diagnosis is easy and the treatment simple and effective.

Innovations in human genetics education. Incorporation of genetics into a problem-based medical school curriculum.

PubMed Central

Swinford, A E; McKeag, D B

1990-01-01

There has been recent interest in the development of problem-based human genetics curricula in U.S. medical schools. The College of Human Medicine at Michigan State University has had a problem-based curriculum since 1974. The vertical integration of genetics within the problem-based curriculum, called "Track II," has recently been revised. On first inspection, the curriculum appeared to lack a significant genetics component; however, on further analysis it was found that many genetics concepts were covered in the biochemistry, microbiology, pathology, and clinical science components. Both basic science concepts and clinical applications of genetics are covered in the curriculum by providing appropriate references for basic concepts and including inherited conditions within the differential diagnosis in the cases studied. Evaluations consist of a multiple-choice content exam and a modified essay exam based on a clinical case, allowing evaluation of both basic concepts and problem-solving ability. This curriculum prepares students to use genetics in a clinical context in their future careers. PMID:2220816

[The discussion of the infiltrative model of chemical knowledge stepping into genetics teaching in agricultural institute or university].

PubMed

Zou, Ping; Luo, Pei-Gao

2010-05-01

Chemistry is an important group of basic courses, while genetics is one of the important major-basic courses in curriculum of many majors in agricultural institutes or universities. In order to establish the linkage between the major course and the basic course, the ability of application of the chemical knowledge previously learned in understanding genetic knowledge in genetics teaching is worthy of discussion for genetics teachers. In this paper, the authors advocate to apply some chemical knowledge previously learned to understand genetic knowledge in genetics teaching with infiltrative model, which could help students learn and understand genetic knowledge more deeply. Analysis of the intrinsic logistic relationship among the knowledge of different courses and construction of the integral knowledge network are useful for students to improve their analytic, comprehensive and logistic abilities. By this way, we could explore a new teaching model to develop the talents with new ideas and comprehensive competence in agricultural fields.

Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

PubMed

Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

2016-04-01

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hepatitis C virus and its cutaneous manifestations: treatment in the direct-acting antiviral era.

PubMed

Wiznia, L E; Laird, M E; Franks, A G

2017-08-01

New all-oral direct-acting antivirals (DAA) have changed the hepatitis C virus (HCV) treatment landscape. Given that dermatologists frequently encounter HCV-infected patients, knowledge of the current treatment options and their utility in treating HCV-associated dermatologic disorders is important. In addition to highlighting the new treatment options, we review four classically HCV-associated dermatologic disorders - mixed cryoglobulinaemia (MC), lichen planus (LP), porphyria cutanea tarda (PCT) and necrolytic acral erythema (NAE) - and examine the role for all-oral direct-acting antiviral (DAA) regimens in their treatment. A literature search of English-language publications was conducted of the PubMed and EMBASE databases using search terms including 'hepatitis C', 'direct acting antivirals', 'cutaneous', 'mixed cryoglobulinemia', 'necrolytic acral erythema', 'lichen planus', 'porphyria cutanea tarda', 'rash', as well as specific drug names, related terms and abbreviations. Currently, limited data exist on the use of DAAs in HCV-infected patients with cutaneous side-effects, although treatment of the underlying HCV is now recommended for nearly all patients, with the new drugs offering much-improved dosage schedules and side-effect profiles. The most data exist for MC, in which several studies suggest that DAAs and achievement of sustained virologic response (SVR) improve cutaneous symptoms. Studies of both older and newer regimens are limited by their small size, retrospective nature, lack of appropriate controls and wide variability in study protocols. Given the strong association, screening for HCV should be considered in patients with MC, LP, PCT and NAE. © 2017 European Academy of Dermatology and Venereology.

Mass spectrometric characterisation of a condensation product between porphobilinogen and indolyl-3-acryloylglycine in urine of patients with acute intermittent porphyria.

PubMed

Marcos, Josep; Ibañez, Maria; Ventura, Rosa; Segura, Jordi; To-Figueras, Jordi; Pozo, Oscar J

2015-07-01

We document the presence of a previously unknown species in the urine of patients with acute intermittent porphyria (AIP). The compound was fully characterised by liquid chromatography tandem mass spectrometry. Interpretation of both full spectrum acquisition and product ion spectra acquired in positive and negative ionisation modes by quadrupole time of flight MS allowed for the identification of a condensation product arising from porphobilinogen (PBG, increased in the urine of AIP patients) and indolyl-3-acryloylglycine (IAG, derived from indolylacrylic acid and present in human urine). The structure was unequivocally confirmed through comparison between the selected reaction monitoring chromatograms obtained from the urinary species and the condensation product qualitatively synthesised in the laboratory. Owing to the large amounts of both PBG and IAG in urine of AIP patients, the possible ex vivo formation of PBG-IAG in urine samples was evaluated. The product was spontaneously formed at room temperature, at 4 °C and even during storage at -20 °C when spiking a control sample with PBG. A positive correlation was found between PBG and PBG-IAG in samples collected from AIP patients. However, no correlation was found between PBG-IAG and IAG. Purified PBG-IAG did not form the characteristic chromogen after application of p-dimethylaminobenzaldehyde in HCl, thus suggesting that the current techniques used to measure PBG in urine of AIP patients based on Ehlrich's reaction do not detect this newly characterised PBG-IAG fraction. Copyright © 2015 John Wiley & Sons, Ltd.

Genes and inheritance.

PubMed

Middelton, L A; Peters, K F

2001-10-01

The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.

[The discussion of the infiltrative model of mathematical knowledge to genetics teaching].

PubMed

Liu, Jun; Luo, Pei-Gao

2011-11-01

Genetics, the core course of biological field, is an importance major-basic course in curriculum of many majors related with biology. Due to strong theoretical and practical as well as abstract of genetics, it is too difficult to study on genetics for many students. At the same time, mathematics is one of the basic courses in curriculum of the major related natural science, which has close relationship with the establishment, development and modification of genetics. In this paper, to establish the intrinsic logistic relationship and construct the integral knowledge network and to help students improving the analytic, comprehensive and logistic abilities, we applied some mathematical infiltrative model genetic knowledge in genetics teaching, which could help students more deeply learn and understand genetic knowledge.

Representing Chronic Disorders of Consciousness:

PubMed Central

Hall, Alice

2014-01-01

This article explores problems of voicelessness in Isabel Allende’s Paula (1995) through a focus on the story of Paula’s illness and subsequent death from porphyria in 1992. I argue that the language, categories and stories through which disorders of consciousness are constructed are central to ethical decision-making and shifting cultural understandings of these conditions. In Paula, Allende uses an experimental, hybrid narrative form that draws on illness narrative, magical realist novel, national history, letters, and memoir to challenge traditional depictions of “coma” and to create a new public space through which these issues of voicelessness can be addressed. PMID:25055709

A CAL Program to Teach the Basic Principles of Genetic Engineering--A Change from the Traditional Approach.

ERIC Educational Resources Information Center

Dewhurst, D. G.; And Others

1989-01-01

An interactive computer-assisted learning program written for the BBC microcomputer to teach the basic principles of genetic engineering is described. Discussed are the hardware requirements software, use of the program, and assessment. (Author/CW)

Genetic Screening: A Unique Game of Survival

ERIC Educational Resources Information Center

Kurvink, Karen; Bowser, Jessica

2004-01-01

A creative learning game that helps students reinforce basic genetic information and facilitate the identification and understanding of the more subtle issues is presented. The basic framework of the game was conceived by a business major taking non-biology major course 'heredity and society-intertwining legacy.

New Genetics

MedlinePlus

... Century-Old Evolutionary Puzzle Computing Genetics Model Organisms RNA Interference The New Genetics is a science education ... the basics of DNA and its molecular cousin RNA, and new directions in genetic research. The New ...

Evaluating a hybrid web-based basic genetics course for health professionals.

PubMed

Wallen, Gwenyth R; Cusack, Georgie; Parada, Suzan; Miller-Davis, Claiborne; Cartledge, Tannia; Yates, Jan

2011-08-01

Health professionals, particularly nurses, continue to struggle with the expanding role of genetics information in the care of their patients. This paper describes an evaluation study of the effectiveness of a hybrid basic genetics course for healthcare professionals combining web-based learning with traditional face-to-face instructional techniques. A multidisciplinary group from the National Institutes of Health (NIH) created "Basic Genetics Education for Healthcare Providers" (BGEHCP). This program combined 7 web-based self-education modules with monthly traditional face-to-face lectures by genetics experts. The course was pilot tested by 186 healthcare providers from various disciplines with 69% (n=129) of the class registrants enrolling in a pre-post evaluation trial. Outcome measures included critical thinking knowledge items and a Web-based Learning Environment Inventory (WEBLEI). Results indicated a significant (p<0.001) change in knowledge scores. WEBLEI scores indicated program effectiveness particularly in the area of convenience, access and the course structure and design. Although significant increases in overall knowledge scores were achieved, scores in content areas surrounding genetic risk identification and ethical issues regarding genetic testing reflected continued gaps in knowledge. Web-based genetics education may help overcome genetics knowledge deficits by providing access for health professionals with diverse schedules in a variety of national and international settings. Published by Elsevier Ltd.

Genetic Influences on Learning Disabilties I: Clinical Genetics.

ERIC Educational Resources Information Center

Smith, Shelley D.; Pennington, Bruce F.

1983-01-01

A discussion of basic genetic principles is followed by a review of selected genetic syndromes involving learning disabilites (such as Noonan Syndrome, Neurofibromatosis, Pheuylketonuria, and cleft lip and palate). Guidelines for securing a genetic evaluation are given. (CL)

Genetics Home Reference: recurrent hydatidiform mole

MedlinePlus

... Rashid Y, Sheridan E, Bonthron DT. Genetic and epigenetic analysis of recurrent hydatidiform mole. Hum Mutat. 2009 ... on PubMed Nguyen NM, Slim R. Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic ...

Low-Dose Hydroxychloroquine is as Effective as Phlebotomy in Treatment of Patients with Porphyria Cutanea Tarda

PubMed Central

Singal, Ashwani K.; Kormos-Hallberg, Csilla; Lee, Chul; Sadagoparamanujam, V.-M.; Grady, James J.; Freeman, Daniel H.; Anderson, Karl E.

2012-01-01

Background & Aims Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase (UROD); it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. Methods We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. Results The time to remission was a median 6.9 months for patients that received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 months for randomized patients), a difference that was not significant (Log Rank P=.06 and P=.95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 0.95–5.06) for all patients. Patients that received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. Conclusions Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. PMID:22985607

Hepatitis C virus core protein triggers abnormal porphyrin metabolism in human hepatocellular carcinoma cells.

PubMed

Nakano, Takafumi; Moriya, Kyoji; Koike, Kazuhiko; Horie, Toshiharu

2018-01-01

Porphyria cutanea tarda (PCT), the most common of the human porphyrias, arises from a deficiency of uroporphyrinogen decarboxylase. Studies have shown a high prevalence of hepatitis C virus (HCV) infection in patients with PCT. While these observations implicate HCV infection as a risk factor for PCT pathogenesis, the mechanism of interaction between the virus and porphyrin metabolism is unknown. This study aimed to assess the effect of HCV core protein on intracellular porphyrin metabolism to elucidate the link between HCV infection and PCT. The accumulation and excretion of porphyrins after treatment with 5-aminolevulinic acid, a porphyrin precursor, were compared between cells stably expressing HCV core protein and controls. Cells expressing HCV core protein had lower amounts of intracellular protoporphyrin IX and heme and had higher amounts of excreted coproporphyrin III, the oxidized form of coproporphyrinogen III, compared with controls. These observations suggest that HCV core protein affects porphyrin metabolism and facilitates the export of excess coproporphyrinogen III and/or coproporphyrin III, possibly via porphyrin transporters. Real-time PCR analysis revealed that the presence of HCV core protein increased the mRNA expression of porphyrin exporters ABCG2 and FLVCR1. Western blot analysis showed a higher expression level of FLVCR1, but not ABCG2, as well as a higher expression level of mature ALAS1, which is the rate-limiting enzyme in the heme synthesis pathway, in HCV core protein-expressing cells compared with controls. The data indicate that HCV core protein induced abnormal intracellular porphyrin metabolism, with an over-excretion of coproporphyrin III. These findings may partially account for the susceptibility of HCV-infected individuals to PCT development.

Nuclear microscopy in biomedical analysis with special emphasis on clinical metal biology

NASA Astrophysics Data System (ADS)

Lindh, Ulf; Frisk, Peter; Nyström, Joakim; Danersund, Antero; Hudecek, Romuald; Lindvall, Anders; Thunell, Stig

1997-07-01

Nuclear microscopy based upon developments in high energy ion beam techniques is by now an accepted technique in many fields of research. The advancements into the biomedical field have, however, been slower than expected. A major factor explaining this tendency is the availability of nuclear microscopy. This paper reviews briefly the biomedical work using nuclear microscopy that has been carried out since the 4 th International Conference on Nuclear Microprobe Technology and Applications held in Shanghai. Nuclear microscopy of isolated individual blood cells from patients adversely affected by metal exposure from dental amalgam has been performed both before and after removal of the metallic fillings. The elemental profile of blood cells was more or less normalised after treatment. Some of these results will be presented to illustrate a medical application. Results from bulk analysis by ICP-MS of erythrocytes and plasma before and after treatment will also be presented to illustrate the difference in information content between these two approaches as well as the need for complementary information in solving biomedical problems. As part of a larger study of acute porphyria, nuclear microscopy of blood cells was included among the 78 laboratory tests. The approach in this study was unbiased in the sense that no hypothesis was formulated as to which laboratory parameters would be the most explanatory for health or disease. Multivariate discriminant analysis was applied to the large amounts of data acquired. This approach led to the hypothesis that oxidative stress increased the synthesis of manganese-dependent superoxide dismutase in the mitochondria of polymorphonuclear leukocytes, explaining the increase of manganese in these cells. Antioxidant therapy was therefore applied to a couple of patients with porphyria, however, without clinical success.

Differential effects of protoporphyrin and uroporphyrin on murine mast cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, H.W.; Gigli, I.; Wasserman, S.I.

1987-03-01

To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with (/sup 3/H)serotonin and (/sup 14/C)arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators ,f 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence ofmore » URO (50-5000 ng/ml) resulted in less than 5% net release. (3H)Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12-myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells.« less

Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda.

PubMed

Stölzel, Ulrich; Köstler, Erich; Schuppan, Detlef; Richter, Matthias; Wollina, Uwe; Doss, Manfred O; Wittekind, Christian; Tannapfel, Andrea

2003-03-01

To examine the role of hemochromatosis (HFE) gene mutations, which are associated with porphyria cutanea tarda (PCT), in the therapeutic response to chloroquine. We retrospectively analyzed a database (Excel version 2001 [Microsoft Excel, Redmond, Wash]; date range of search, 1985-1999) of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities, and serum iron markers. Serum samples and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine. Academic teaching hospital. For treatment, low-dose chloroquine diphosphate, 125 to 250 mg twice weekly, was used during a median time of 16 months (range, 12-26 months). Of the 62 German patients with PCT, 37 (60%) carries HFE mutations. Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (P<.001) in the 24 patients (39%) with HFE wild type as well as in 35 HFE heterozygous patients with PCT (56%). Decreases of serum iron markers following chloroquine therapy were limited to patients with PCT and HFE wild type. All patients homozygous for the C282Y mutation (3 [5%] of 62) had high serum iron, ferritin, and transferrin saturation and failed to respond to chloroquine treatment. The therapeutic response to chloroquine was not compromised by C282Y heterozygosity and compound heterozygosity of HFE mutations. Because HFE C282Y homozygotes (+/+) did not respond to chloroquine and a decrease in serum iron concentration was limited to patients with PCT and HFE wild type, phlebotomy should be first-line therapy in patients with PCT and HFE mutations.

Imaging Genetics

ERIC Educational Resources Information Center

Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

2009-01-01

Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

Genetic algorithms

NASA Technical Reports Server (NTRS)

Wang, Lui; Bayer, Steven E.

1991-01-01

Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

[Skin and chronic kidney disease].

PubMed

Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio

2014-01-01

Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process.

Biochemical Characterization of Porphobilinogen Deaminase–Deficient Mice During Phenobarbital Induction of Heme Synthesis and the Effect of Enzyme Replacement

PubMed Central

Johansson, Annika; Möller, Christer; Fogh, Jens; Harper, Pauline

2003-01-01

Acute intermittent porphyria (AIP) is a genetic disorder caused by a deficiency of porphobilinogen deaminase (PBGD), the 3rd enzyme in heme synthesis. It is clinically characterized by acute attacks of neuropsychiatric symptoms and biochemically by increased urinary excretion of the porphyrin precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA). A mouse model that is partially deficient in PBGD and biochemically mimics AIP after induction of the hepatic ALA synthase by phenobarbital was used in this study to identify the site of formation of the presumably toxic porphyrin precursors and study the effect of enzyme-replacement therapy by using recombinant human PBGD (rhPBGD). After 4 d of phenobarbital administration, high levels of PBG and ALA were found in liver, kidney, plasma, and urine of the PBGD-deficient mice. The administration of rhPBGD intravenously or subcutaneously after a 4-d phenobarbital induction was shown to lower the PBG level in plasma in a dose-dependent manner with maximal effect seen after 30 min and 2 h, respectively. Injection of rhPBGD subcutaneously twice daily during a 4-d phenobarbital induction reduced urinary PBG excretion to 25% of the levels found in PBGD-deficient mice administered with only phenobarbital. This study points to the liver as the main producer of PBG and ALA in the phenobarbital-induced PBGD-deficient mice and demonstrates efficient removal of accumulated PBG in plasma and urine by enzyme-replacement therapy. PMID:15208740

Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review.

PubMed

Ferreli, Caterina; Gasparini, Giulia; Parodi, Aurora; Cozzani, Emanuele; Rongioletti, Franco; Atzori, Laura

2017-12-01

Scleroderma refers to an autoimmune connective tissue fibrosing disease, including three different subsets: localized scleroderma, limited cutaneous systemic sclerosis, and diffuse cutaneous systemic sclerosis with divergent patterns of organ involvement, autoantibody profiles, management, and prognostic implications. Although systemic sclerosis is considered the disease prototype that causes cutaneous sclerosis, there are many other conditions that can mimic and be confused with SSc. They can be classified into immune-mediated/inflammatory, immune-mediated/inflammatory with abnormal deposit (mucinoses), genetic, drug-induced and toxic, metabolic, panniculitis/vascular, and (para)neoplastic disorders according to clinico-pathological and pathogenetic correlations. This article reviews the clinical presentation with emphasis on cutaneous disease, etiopathogenesis, diagnosis, and treatment options available for the different forms of scleroderma firstly and for scleroderma-like disorders, including scleromyxedema, scleredema, nephrogenic systemic fibrosis, eosinophilic fasciitis, chronic graft-versus-host disease, porphyria cutanea tarda, diabetic stiff-hand syndrome (diabetic cheiroartropathy), and other minor forms. This latter group of conditions, termed also scleroderma mimics, sclerodermiform diseases, or pseudosclerodermas, shares the common thread of skin thickening but presents with distinct cutaneous manifestations, skin histology, and systemic implications or disease associations, differentiating each entity from the others and from scleroderma. The lack of Raynaud's phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies is also important diagnostic clues. As cutaneous involvement is the earliest, most frequent and characteristic manifestation of scleroderma and sclerodermoid disorders, dermatologists are often the first-line doctors who must be able to promptly recognize skin symptoms to provide the affected patient a correct diagnosis and appropriate management.

Genetic and Genomic Toolbox of Zea mays

PubMed Central

Nannas, Natalie J.; Dawe, R. Kelly

2015-01-01

Maize has a long history of genetic and genomic tool development and is considered one of the most accessible higher plant systems. With a fully sequenced genome, a suite of cytogenetic tools, methods for both forward and reverse genetics, and characterized phenotype markers, maize is amenable to studying questions beyond plant biology. Major discoveries in the areas of transposons, imprinting, and chromosome biology came from work in maize. Moving forward in the post-genomic era, this classic model system will continue to be at the forefront of basic biological study. In this review, we outline the basics of working with maize and describe its rich genetic toolbox. PMID:25740912

Teacher-to-Teacher: An Annotated Bibliography on DNA and Genetic Engineering.

ERIC Educational Resources Information Center

Mertens, Thomas R., Comp.

1984-01-01

Presented is an annotated bibliography of 24 books on DNA and genetic engineering. Areas considered in these books include: basic biological concepts to help understand advances in genetic engineering; applications of genetic engineering; social, legal, and moral issues of genetic engineering; and historical aspects leading to advances in…

Integrating population genetics and conservation biology in the era of genomics.

PubMed

Ouborg, N Joop

2010-02-23

As one of the final activities of the ESF-CONGEN Networking programme, a conference entitled 'Integrating Population Genetics and Conservation Biology' was held at Trondheim, Norway, from 23 to 26 May 2009. Conference speakers and poster presenters gave a display of the state-of-the-art developments in the field of conservation genetics. Over the five-year running period of the successful ESF-CONGEN Networking programme, much progress has been made in theoretical approaches, basic research on inbreeding depression and other genetic processes associated with habitat fragmentation and conservation issues, and with applying principles of conservation genetics in the conservation of many species. Future perspectives were also discussed in the conference, and it was concluded that conservation genetics is evolving into conservation genomics, while at the same time basic and applied research on threatened species and populations from a population genetic point of view continues to be emphasized.

Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research.

PubMed

Manolio, Teri A; Fowler, Douglas M; Starita, Lea M; Haendel, Melissa A; MacArthur, Daniel G; Biesecker, Leslie G; Worthey, Elizabeth; Chisholm, Rex L; Green, Eric D; Jacob, Howard J; McLeod, Howard L; Roden, Dan; Rodriguez, Laura Lyman; Williams, Marc S; Cooper, Gregory M; Cox, Nancy J; Herman, Gail E; Kingsmore, Stephen; Lo, Cecilia; Lutz, Cathleen; MacRae, Calum A; Nussbaum, Robert L; Ordovas, Jose M; Ramos, Erin M; Robinson, Peter N; Rubinstein, Wendy S; Seidman, Christine; Stranger, Barbara E; Wang, Haoyi; Westerfield, Monte; Bult, Carol

2017-03-23

Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations, we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, and promoting data sharing. Published by Elsevier Inc.

Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research

PubMed Central

Manolio, Teri A.; Fowler, Douglas M.; Starita, Lea M.; Haendel, Melissa A.; MacArthur, Daniel G.; Biesecker, Leslie G.; Worthey, Elizabeth; Chisholm, Rex L.; Green, Eric D.; Jacob, Howard J.; McLeod, Howard L.; Roden, Dan; Rodriguez, Laura Lyman; Williams, Marc S.; Cooper, Gregory M.; Cox, Nancy J.; Herman, Gail E.; Kingsmore, Stephen; Lo, Cecilia; Lutz, Cathleen; MacRae, Calum A.; Nussbaum, Robert L.; Ordovas, Jose M.; Ramos, Erin M.; Robinson, Peter N.; Rubinstein, Wendy S.; Seidman, Christine; Stranger, Barbara E.; Wang, Haoyi; Westerfield, Monte; Bult, Carol

2017-01-01

Summary Genome sequencing has revolutionized the diagnosis of genetic diseases. Close collaborations between basic scientists and clinical genomicists are now needed to link genetic variants with disease causation. To facilitate such collaborations we recommend prioritizing clinically relevant genes for functional studies, developing reference variant-phenotype databases, adopting phenotype description standards, and promoting data sharing. PMID:28340351

Unraveling the genetic structure of Brazilian commercial sugarcane cultivars through microsatellite markers

PubMed Central

Manechini, João Ricardo Vieira; da Costa, Juliana Borges; Pereira, Bruna Turcatto; Carlini-Garcia, Luciana Aparecida; Xavier, Mauro Alexandre; Landell, Marcos Guimarães de Andrade

2018-01-01

The Brazilian sugarcane industry plays an important role in the worldwide supply of sugar and ethanol. Investigation into the genetic structure of current commercial cultivars and comparisons to the main ancestor species allow sugarcane breeding programs to better manage crosses and germplasm banks as well as to promote its rational use. In the present study, the genetic structure of a group of Brazilian cultivars currently grown by commercial producers was assessed through microsatellite markers and contrasted with a group of basic germplasm mainly composed of Saccharum officinarum and S. spontaneum accessions. A total of 285 alleles was obtained by a set of 12 SSRs primer pairs that taken together were able to efficiently distinguish and capture the genetic variability of sugarcane commercial cultivars and basic germplasm accessions allowing its application in a fast and cost-effective way for routine cultivar identification and management of sugarcane germplasm banks. Allelic distribution revealed that 97.6% of the cultivar alleles were found in the basic germplasm while 42% of the basic germplasm alleles were absent in cultivars. Of the absent alleles, 3% was exclusive to S. officinarum, 33% to S. spontaneum and 19% to other species/exotic hybrids. We found strong genetic differentiation between the Brazilian commercial cultivars and the two main species (S. officinarum: Φ^ST = 0.211 and S. spontaneum: Φ^ST = 0.216, P<0.001), and significant contribution of the latter in the genetic variability of commercial cultivars. Average dissimilarity within cultivars was 1.2 and 1.4 times lower than that within S. officinarum and S. spontaneum. Genetic divergence found between cultivars and S. spontaneum accessions has practical applications for energy cane breeding programs as the choice of more divergent parents will maximize the frequency of transgressive individuals in the progeny. PMID:29684082

Cleft Palate-Craniofacial Journal 50th anniversary editorial board commentary: anatomy, basic sciences, and genetics--then and now.

PubMed

Mooney, Mark P; Cooper, Gregory M; Marazita, Mary L

2014-05-01

To celebrate the 50th year of the Cleft Palate-Craniofacial Journal we look back to where we started in 1964 and where we are now, and we speculate about directions for the future in a "Then and Now" editorial series. This editorial examines changing trends and perspectives in anatomical, basic science, and genetic studies published in this 50-year interval. In volume 1 there were 45 total papers, seven (16%) of which were peer-reviewed basic science and genetic articles published: four in anatomy, three in craniofacial biology, and none in genetics. In contrast, in volume 50, of 113 articles there were 47 (42%) peer-reviewed basic science and genetic articles published: 30 in anatomy, five in craniofacial biology, and 12 in genetics. Topical analysis of published manuscripts then and now reveal that similar topics in anatomy and craniofacial biology are still being researched today (e.g., phenotypic variability, optimal timing of surgery, presurgical orthopedics, bone grafting); whereas, most of the more recent papers use advanced technology to address old questions. In contrast, genetic publications have clearly increased in frequency during the last 50 years, which parallels advances in the field during this time. However, all of us have noticed that the more "cutting-edge" papers in these areas are not being submitted for publication to the journal, but instead to discipline-specific journals. Concerted efforts are therefore indicated to attract and publish these cutting-edge papers in order to keep the Cleft Palate-Craniofacial Journal in the forefront of orofacial cleft and craniofacial anomaly research and to provide a valuable service to American Cleft Palate-Craniofacial Association members.

Unraveling the genetic structure of Brazilian commercial sugarcane cultivars through microsatellite markers.

PubMed

Manechini, João Ricardo Vieira; da Costa, Juliana Borges; Pereira, Bruna Turcatto; Carlini-Garcia, Luciana Aparecida; Xavier, Mauro Alexandre; Landell, Marcos Guimarães de Andrade; Pinto, Luciana Rossini

2018-01-01

The Brazilian sugarcane industry plays an important role in the worldwide supply of sugar and ethanol. Investigation into the genetic structure of current commercial cultivars and comparisons to the main ancestor species allow sugarcane breeding programs to better manage crosses and germplasm banks as well as to promote its rational use. In the present study, the genetic structure of a group of Brazilian cultivars currently grown by commercial producers was assessed through microsatellite markers and contrasted with a group of basic germplasm mainly composed of Saccharum officinarum and S. spontaneum accessions. A total of 285 alleles was obtained by a set of 12 SSRs primer pairs that taken together were able to efficiently distinguish and capture the genetic variability of sugarcane commercial cultivars and basic germplasm accessions allowing its application in a fast and cost-effective way for routine cultivar identification and management of sugarcane germplasm banks. Allelic distribution revealed that 97.6% of the cultivar alleles were found in the basic germplasm while 42% of the basic germplasm alleles were absent in cultivars. Of the absent alleles, 3% was exclusive to S. officinarum, 33% to S. spontaneum and 19% to other species/exotic hybrids. We found strong genetic differentiation between the Brazilian commercial cultivars and the two main species (S. officinarum: [Formula: see text] = 0.211 and S. spontaneum: [Formula: see text] = 0.216, P<0.001), and significant contribution of the latter in the genetic variability of commercial cultivars. Average dissimilarity within cultivars was 1.2 and 1.4 times lower than that within S. officinarum and S. spontaneum. Genetic divergence found between cultivars and S. spontaneum accessions has practical applications for energy cane breeding programs as the choice of more divergent parents will maximize the frequency of transgressive individuals in the progeny.

Lessons from 25 years of genetic mapping in onion: where next?

USDA-ARS?s Scientific Manuscript database

Genetic maps are useful tools for both basic research and plant improvement. Close association of genetic markers with genes controlling economically important traits allows for indirect selection, avoiding often time-consuming and expensive phenotypic evaluations. As a result, detailed genetic maps...

Basic-Education Mexican Teachers' Knowledge of Biotechnology and Attitudes about the Consumption of Genetically Modified Foods

ERIC Educational Resources Information Center

Jiménez-Salas, Zacarías; Campos-Góngora, Eduardo; González-Martínez, Blanca E.; Tijerina-Sáenz, Alexandra; Escamilla-Méndez, Angélica D.; Ramírez-López, Erik

2017-01-01

Over the past few years, a new research field has emerged, focusing on the social-scientific criteria for the study of opinions toward genetically modified foods (GMFs), since these may be limiting factors for the success or failure of these products. Basic education is the first step in the Mexican education system, and teachers may wield an…

Nurses' knowledge and educational needs regarding genetics.

PubMed

Seven, Memnun; Akyüz, Aygül; Elbüken, Burcu; Skirton, Heather; Öztürk, Hatice

2015-03-01

Nurses now require a basic knowledge of genetics to provide patient care in a range of settings. To determine Turkish registered nurses' current knowledge and educational needs in relation to genetics. A descriptive, cross-sectional study. Turkish registered nurses working in a university hospital in Turkey were recruited. All registered nurses were invited to participate and 175 completed the study. The survey instrument, basic knowledge of health genetics, confidence in knowledge and the nurses' need for genetics education were used to collect data. The majority (81.1%, n=142) of participants indicated that genetics was not taught during their degree program, although 53.1% to 96% of respondents felt confident in defining different genetic concepts. The average genetics knowledge score was 6.89±1.99 of a possible 11 (range 0-11). The majority (70.3%) expressed a strong wish to attend a continuing nursing education program in genetics. The study shows that although Turkish nurses are not sufficiently knowledgeable to apply genetics in practice, they are willing to have more education to support their care of patients. Nurses need to have more education related to genetics in accordance with advances in human genetics to optimize health care. Copyright © 2014 Elsevier Ltd. All rights reserved.

Drosophila Genetic Resource and Stock Center; The National BioResource Project.

PubMed

Yamamoto, Masa-Toshi

2010-01-01

The fruit fly, Drosophila melanogaster, is not categorized as a laboratory animal, but it is recognised as one of the most important model organisms for basic biology, life science, and biomedical research. This tiny fly continues to occupy a core place in genetics and genomic approaches to studies of biology and medicine. The basic principles of genetics, including the variations of phenotypes, mutations, genetic linkage, meiotic chromosome segregation, chromosome aberrations, recombination, and precise mapping of genes by genetic as well as cytological means, were all derived from studies of Drosophila. Recombinant DNA technology was developed in the 1970s and Drosophila DNA was the first among multicellular organisms to be cloned. It provided a detailed characterization of genes in combination of classical cytogenetic data. Drosophila thus became the pioneering model organism for various fields of life science research into multicellular organisms. Here, I briefly describe the history of Drosophila research and provide a few examples of the application of the abundant genetic resources of Drosophila to basic biology and medical investigations. A Japanese national project, the National BioResource Project (NBRP) for collection, maintainance, and provision of Drosophila resources, that is well known and admired by researchers in other countries as an important project, is also briefly described.

Teaching Mendelian Genetics with the Computer.

ERIC Educational Resources Information Center

Small, James W., Jr.

Students in general undergraduate courses in both biology and genetics seem to have great difficulty mastering the basic concepts of Mendelian Genetics and solving even simple problems. In an attempt to correct this situation, students in both courses at Rollins College were introduced to three simulation models of the genetics of the fruit…

Insurance and genetic testing: where are we now?

PubMed Central

Ostrer, H; Allen, W; Crandall, L A; Moseley, R E; Dewar, M A; Nye, D; McCrary, S V

1993-01-01

Basic research will spur development of genetic tests that are capable of presymptomatic prediction of disease, disability, and premature death in presently asymptomatic individuals. Concerns have been expressed about potential harms related to the use of genetic test results, especially loss of confidentiality, eugenics, and discrimination. Existing laws and administrative policies may not be sufficient to assure that genetic information is used fairly. To provide factual information and conceptual principles upon which sound social policy can be based, the Human Genome Initiative established an Ethical, Legal, and Social Issues Program. Among the first areas to be identified as a priority for study was insurance. This paper provides a review of life, health, and disability insurance systems, including basic principles, risk classification, and market and regulatory issues, and examines the potential impact of genetic information on the insurance industry. PMID:8447322

Proceedings of the symposium on isozymes of North American forest trees and forest insects; July 27, 1979; Berkeley, California

Treesearch

M. Thompson Conkle

1981-01-01

These 10 symposium papers discuss gene resource management, basic genetics, genetic variation between and within tree species, genetic variability and growth, comparisons of tree life history characteristics, genetic variation in forest insects, breeding systems, and applied uses of isozymes in breeding programs.

Gas chromatography-mass spectrometry profiling of steroids in urine of patients with acute intermittent porphyria.

PubMed

Casals, Gregori; Marcos, Josep; Pozo, Óscar J; Aguilera, Paula; Herrero, Carmen; To-Figueras, Jordi

2013-06-01

Acute intermittent porphyria (AIP) is an autosomal dominant disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers may present acute neurovisceral attacks with hepatic overproduction of heme-precursors. In some patients, remission of the acute symptoms leads to long-term hepatic metabolic abnormalities. In this study, gas chromatography-mass spectrometry (GC/MS) was used to investigate urinary steroid metabolome of AIP patients. Steroid profiling in urine was performed in a group of AIP patients with biochemically active disease (n=22) and healthy controls (n = 20). Five asymptomatic AIP family carriers were also studied. Commonly used ratios for the evaluation of disturbances in the steroid metabolism were calculated. We found that etiocholanolone/androsterone and tetrahydrocortisol/5α-tetrahydrocortisol (THF/5α-THF) metabolic ratios were significantly increased in the urine of AIP patients compared to controls (2.3 ± 0.3 vs 0.8 ± 0.1; p < 0.001 and 2.9 ± 0.7 vs 0.9 ± 0.1; p < 0.01). The (THF+5α-THF)/tetrahydrocortisone ratio was reduced among the AIP patients (p < 0.01). Quantification of the steroid absolute concentrations showed that these variations were due to a decrease of the 5α metabolites. Other ratios, like cortisol/cortisone and 6β-hydroxycortisol/cortisol in the free steroid fraction did not show differences between patients and controls. All ratios were normal among the family carriers. A significant number of AIP patients present a basal decrease of steroid 5α-reductase activity in the liver. The deficiency may be related to malnutrition and hepatic energy misbalance associated with active AIP. Urinary steroid profiling by GC/MS may be a valuable tool to assess hepatic metabolome in AIP. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Comparative use of InDel and SSR markers in deciphering the interspecific structure of cultivated citrus genetic diversity: a perspective for genetic association studies.

PubMed

García-Lor, Andrés; Luro, François; Navarro, Luis; Ollitrault, Patrick

2012-01-01

Genetic stratification associated with domestication history is a key parameter for estimating the pertinence of genetic association study within a gene pool. Previous molecular and phenotypic studies have shown that most of the diversity of cultivated citrus results from recombination between three main species: C. medica (citron), C. reticulata (mandarin) and C. maxima (pummelo). However, the precise contribution of each of these basic species to the genomes of secondary cultivated species, such as C. sinensis (sweet orange), C. limon (lemon), C. aurantium (sour orange), C. paradisi (grapefruit) and recent hybrids is unknown. Our study focused on: (1) the development of insertion-deletion (InDel) markers and their comparison with SSR markers for use in genetic diversity and phylogenetic studies; (2) the analysis of the contributions of basic taxa to the genomes of secondary species and modern cultivars and (3) the description of the organisation of the Citrus gene pool, to evaluate how genetic association studies should be done at the cultivated Citrus gene pool level. InDel markers appear to be better phylogenetic markers for tracing the contributions of the three ancestral species, whereas SSR markers are more useful for intraspecific diversity analysis. Most of the genetic organisation of the Citrus gene pool is related to the differentiation between C. reticulata, C. maxima and C. medica. High and generalised LD was observed, probably due to the initial differentiation between the basic species and a limited number of interspecific recombinations. This structure precludes association genetic studies at the genus level without developing additional recombinant populations from interspecific hybrids. Association genetic studies should also be affordable at intraspecific level in a less structured pool such as C. reticulata.

Medical genetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorde, L.B.; Carey, J.C.; White, R.L.

This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells

PubMed Central

Sahoo, Swagatika; Thiele, Ines

2013-01-01

Small intestinal epithelial cells (sIECs) have a significant share in whole body metabolism as they perform enzymatic digestion and absorption of nutrients. Furthermore, the diet plays a key role in a number of complex diseases including obesity and diabetes. The impact of diet and altered genetic backgrounds on human metabolism may be studied by using computational modeling. A metabolic reconstruction of human sIECs was manually assembled using the literature. The resulting sIEC model was subjected to two different diets to obtain condition-specific metabolic models. Fifty defined metabolic tasks evaluated the functionalities of these models, along with the respective secretion profiles, which distinguished between impacts of different dietary regimes. Under the average American diet, the sIEC model resulted in higher secretion flux for metabolites implicated in metabolic syndrome. In addition, enzymopathies were analyzed in the context of the sIEC metabolism. Computed results were compared with reported gastrointestinal (GI) pathologies and biochemical defects as well as with biomarker patterns used in their diagnosis. Based on our simulations, we propose that (i) sIEC metabolism is perturbed by numerous enzymopathies, which can be used to study cellular adaptive mechanisms specific for such disorders, and in the identification of novel co-morbidities, (ii) porphyrias are associated with both heme synthesis and degradation and (iii) disturbed intestinal gamma-aminobutyric acid synthesis may be linked to neurological manifestations of various enzymopathies. Taken together, the sIEC model represents a comprehensive, biochemically accurate platform for studying the function of sIEC and their role in whole body metabolism. PMID:23492669

[Prospect and application of microsatellite population genetics in study of geoherbs].

PubMed

Zhang, Wen-Jing; Zhang, Yong-Qing; Yuan, Qing-Jun; Huang, Lu-Qi; Jiang, Dan; Jing, Li

2013-12-01

The author introduces the basic concepts of microsatellite and population genetics and its characteristics, expounds the application of these theories for population genetic structure and genetic diversity, gene flow and evolutionary significant unit ESU division research. This paper discuss its applicationin study of genetic causes, origin of cultivation, different regional origins of geoherbs, aiming at providing a new theory and method for geoherbs.

Can Genetics and Genomics Nursing Competencies Be Successfully Taught in a Prenursing Microbiology Course?

PubMed Central

Shuster, Michèle

2011-01-01

In recognition of the entry into the era of personalized medicine, a new set of genetics and genomics competencies for nurses was introduced in 2006. Since then, there have been a number of reports about the critical importance of these competencies for nursing practices and about the challenges of addressing these competencies in the preservice (basic science) nursing curriculum. At least one suggestion has been made to infuse genetics and genomics throughout the basic science curriculum for prenursing students. Based on this call and a review of the competencies, this study sought to assess the impact of incorporation of genetics and genomics content into a prenursing microbiology course. Broadly, two areas that address the competencies were incorporated into the course: 1) the biological basis and implications of genetic diversity and 2) the technological aspects of assessing genetic diversity in bacteria and viruses. These areas address how genetics and genomics contribute to healthcare, including diagnostics and selection of treatment. Analysis of learning gains suggests that genetics and genomics content can be learned as effectively as microbiology content in this setting. Future studies are needed to explore the most effective ways to introduce genetics and genomics technology into the prenursing curriculum. PMID:21633070

The art and design of genetic screens: maize

USDA-ARS?s Scientific Manuscript database

Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible...

Basic glossary on genetic epidemiology.

PubMed

Malats, N; Calafell, F

2003-07-01

This is the second of a series of three glossaries on genetic concepts used in epidemiological research that the journal is publishing with the objective of helping the reader "walk" around the journal.

PCB residues in the adipose tissue of the population of Barcelona (Spain)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomez-Catalan, J.; Sabroso, M.; To-Figueras, J.

1991-10-01

Polychlorinated biphenyls (PCBs) are a class of aryl halides widely distributed in the environment. Although production has virtually ceased, and most industrial applications (capacitors, transformers, hydraulic fluids, lubricants, etc) are severely restricted, they are one of the most ubiquitous and persistent environmental pollutants. Several toxic effects caused by PCBs have been described including: liver enlargement, hepatomegalocytosis, acne, lymphoid atrophy, immunosuppression, tumor promotion, porphyria. This work continues the authors' previous reports about organochlorine residues in human tissues of some Spanish populations, that showed high levels of some residues, specially of hexachlorobenzene (HCB). PCBs pattern and concentration in the adipose tissue ofmore » the inhabitants of an urban and industrial area (Barcelona) were determined.« less

From drug to protein: using yeast genetics for high-throughput target discovery.

PubMed

Armour, Christopher D; Lum, Pek Yee

2005-02-01

The budding yeast Saccharomyces cerevisiae has long been an effective eukaryotic model system for understanding basic cellular processes. The genetic tractability and ease of manipulation in the laboratory make yeast well suited for large-scale chemical and genetic screens. Several recent studies describing the use of yeast genetics for high-throughput drug target identification are discussed in this review.

How to Design a Genetic Mating Scheme: A Basic Training Package for Drosophila Genetics

PubMed Central

Roote, John; Prokop, Andreas

2013-01-01

Drosophila melanogaster is a powerful model organism for biological research. The essential and common instrument of fly research is genetics, the art of applying Mendelian rules in the specific context of Drosophila with its unique classical genetic tools and the breadth of modern genetic tools and strategies brought in by molecular biology, transgenic technologies and the use of recombinases. Training newcomers to fly genetics is a complex and time-consuming task but too important to be left to chance. Surprisingly, suitable training resources for beginners currently are not available. Here we provide a training package for basic Drosophila genetics, designed to ensure that basic knowledge on all key areas is covered while reducing the time invested by trainers. First, a manual introduces to fly history, rationale for mating schemes, fly handling, Mendelian rules in fly, markers and balancers, mating scheme design, and transgenic technologies. Its self-study is followed by a practical training session on gender and marker selection, introducing real flies under the dissecting microscope. Next, through self-study of a PowerPoint presentation, trainees are guided step-by-step through a mating scheme. Finally, to consolidate knowledge, trainees are asked to design similar mating schemes reflecting routine tasks in a fly laboratory. This exercise requires individual feedback but also provides unique opportunities for trainers to spot weaknesses and strengths of each trainee and take remedial action. This training package is being successfully applied at the Manchester fly facility and may serve as a model for further training resources covering other aspects of fly research. PMID:23390611

Basic Genetics: A Human Approach.

ERIC Educational Resources Information Center

Biological Sciences Curriculum Study, Colorado Springs, CO. Center for Education in Human and Medical Genetics.

This document (which has the form of a magazine) provides a variety of articles, stories, editorials, letters, interviews, and other types of magazine features (such as book reviews) which focus on human genetics. In addition to providing information about the principles of genetics, nearly all of the sections in the "magazine" address moral,…

How to Teach Procedures, Problem Solving, and Concepts in Microbial Genetics

ERIC Educational Resources Information Center

Bainbridge, Brian W.

1977-01-01

Flow-diagrams, algorithms, decision logic tables, and concept maps are presented in detail as methods for teaching practical procedures, problem solving, and basic concepts in microbial genetics. It is suggested that the flexible use of these methods should lead to an improved understanding of microbial genetics. (Author/MA)

Reviews in genetics and cytology. I. Plant breeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, C J

1963-03-01

A review of recent plant breeding research in cytology and genetics indicates that there have been many significant accomplisments that have greatly extended our basic knowledge in this field. Major developments are reviewed.

Genetics of Hearing Loss

MedlinePlus

... Hearing Loss Homepage Basics Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2016 2015 2014 2013 ...

Computer Center: BASIC String Models of Genetic Information Transfer.

ERIC Educational Resources Information Center

Spain, James D., Ed.

1984-01-01

Discusses some of the major genetic information processes which may be modeled by computer program string manipulation, focusing on replication and transcription. Also discusses instructional applications of using string models. (JN)

[The development of molecular human genetics and its significance for perspectives of modern medicine].

PubMed

Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

1989-01-01

The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

ACOG Technology Assessment No. 11: Genetics and molecular diagnostic testing.

PubMed

2014-02-01

Human genetics and molecular testing are playing an increasingly important role in medicine, including obstetric and gynecologic practice. As the genetic basis for reproductive disorders, common diseases, and cancer is elucidated with improved molecular technology, genetic testing opportunities are expanding and influencing treatment options and prevention strategies. It is essential that obstetrician-gynecologists be aware of advances in the understanding of genetic disease and the fundamental principles of genetic screening and molecular testing as genetics becomes a more integral part of routine medical practice. This document reviews the basics of genetic transmission and genetic technologies in current use.

Genetic Determinism in the Genetics Curriculum: An Exploratory Study of the Effects of Mendelian and Weldonian Emphases

ERIC Educational Resources Information Center

Jamieson, Annie; Radick, Gregory

2017-01-01

Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is…

Genetics

USDA-ARS?s Scientific Manuscript database

The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

Using the Eastern Hellbender Salamander in a High School Genetics & Ecological Conservation Activity

ERIC Educational Resources Information Center

Chudyk, Sarah; McMillan, Amy; Lange, Catherine

2014-01-01

This article contains an original 5E lesson plan developed from conservation genetics research on the giant North American hellbender salamander, Cryptobranchus alleganiensis alleganiensis. The lesson plan provides background information on the hellbender, reviews basic genetics, and exposes students to the scientific process that is used during…

Coverage of genetic technologies under national health reform.

PubMed Central

Mehlman, M. J.; Botkin, J. R.; Scarrow, A.; Woodhall, A.; Kass, J.; Siebenschuh, E.

1994-01-01

This article examines the extent to which the technologies expected to emerge from genetic research are likely to be covered under Government-mandated health insurance programs such as those being proposed by advocates of national health reform. Genetic technologies are divided into three broad categories; genetic information services, including screening, testing, and counseling; experimental technologies; and gene therapy. This article concludes that coverage of these technologies under national health reform is uncertain. The basic benefits packages provided for in the major health reform plans are likely to provide partial coverage of experimental technologies; relatively broad coverage of information services; and varying coverage of gene therapies, on the basis of an evaluation of their costs, benefits, and the degree to which they raise objections on political and religious grounds. Genetic services that are not included in the basic benefits package will be available only to those who can purchase supplemental insurance or to those who can purchase the services with personal funds. The resulting multitiered system of access to genetic services raises serious questions of fairness. PMID:7977343

PopSc: Computing Toolkit for Basic Statistics of Molecular Population Genetics Simultaneously Implemented in Web-Based Calculator, Python and R

PubMed Central

Huang, Ying; Li, Cao; Liu, Linhai; Jia, Xianbo; Lai, Song-Jia

2016-01-01

Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis. PMID:27792763

PopSc: Computing Toolkit for Basic Statistics of Molecular Population Genetics Simultaneously Implemented in Web-Based Calculator, Python and R.

PubMed

Chen, Shi-Yi; Deng, Feilong; Huang, Ying; Li, Cao; Liu, Linhai; Jia, Xianbo; Lai, Song-Jia

2016-01-01

Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis.

Standards of Practice: Applying Genetics and Genomics Resources to Oncology
.

PubMed

Kerber, Alice S; Ledbetter, Nancy J

2017-04-01

Knowledge about genetics and genomics and its application to oncology care is rapidly expanding and evolving. As a result, oncology nurses at all levels must develop and maintain their knowledge of genetics and genomics, as well as be aware of resources to guide practice. This article focuses on implementation of the standards described in the updated Genetics/Genomics Nursing: Scope and Standards of Practice by the basic practitioner.
.

Current genetic methodologies in the identification of disaster victims and in forensic analysis.

PubMed

Ziętkiewicz, Ewa; Witt, Magdalena; Daca, Patrycja; Zebracka-Gala, Jadwiga; Goniewicz, Mariusz; Jarząb, Barbara; Witt, Michał

2012-02-01

This review presents the basic problems and currently available molecular techniques used for genetic profiling in disaster victim identification (DVI). The environmental conditions of a mass disaster often result in severe fragmentation, decomposition and intermixing of the remains of victims. In such cases, traditional identification based on the anthropological and physical characteristics of the victims is frequently inconclusive. This is the reason why DNA profiling became the gold standard for victim identification in mass-casualty incidents (MCIs) or any forensic cases where human remains are highly fragmented and/or degraded beyond recognition. The review provides general information about the sources of genetic material for DNA profiling, the genetic markers routinely used during genetic profiling (STR markers, mtDNA and single-nucleotide polymorphisms [SNP]) and the basic statistical approaches used in DNA-based disaster victim identification. Automated technological platforms that allow the simultaneous analysis of a multitude of genetic markers used in genetic identification (oligonucleotide microarray techniques and next-generation sequencing) are also presented. Forensic and population databases containing information on human variability, routinely used for statistical analyses, are discussed. The final part of this review is focused on recent developments, which offer particularly promising tools for forensic applications (mRNA analysis, transcriptome variation in individuals/populations and genetic profiling of specific cells separated from mixtures).

Molecular basis of angiosperm tree architecture

USDA-ARS?s Scientific Manuscript database

The shoot architecture of trees greatly impacts orchard and forest management methods. Amassing greater knowledge of the molecular genetics behind tree form can benefit these industries as well as contribute to basic knowledge of plant developmental biology. This review covers basic components of ...

[MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

PubMed

Liu, Ren-Hu; Meng, Jin-Ling

2003-05-01

MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor.

Grocery Store Genetics: A PCR-Based Genetics Lab that Links Genotype to Phenotype

ERIC Educational Resources Information Center

Briju, Betsy J.; Wyatt, Sarah E.

2015-01-01

Instructors often present Mendelian genetics and molecular biology separately. As a result, students often fail to connect the two topics in a tangible manner. We have adopted a simple experiment to help link these two important topics in a basic biology course, using red and white onions bought from a local grocery store. A lack of red coloration…

SNP_tools: A compact tool package for analysis and conversion of genotype data for MS-Excel

PubMed Central

Chen, Bowang; Wilkening, Stefan; Drechsel, Marion; Hemminki, Kari

2009-01-01

Background Single nucleotide polymorphism (SNP) genotyping is a major activity in biomedical research. Scientists prefer to have a facile access to the results which may require conversions between data formats. First hand SNP data is often entered in or saved in the MS-Excel format, but this software lacks genetic and epidemiological related functions. A general tool to do basic genetic and epidemiological analysis and data conversion for MS-Excel is needed. Findings The SNP_tools package is prepared as an add-in for MS-Excel. The code is written in Visual Basic for Application, embedded in the Microsoft Office package. This add-in is an easy to use tool for users with basic computer knowledge (and requirements for basic statistical analysis). Conclusion Our implementation for Microsoft Excel 2000-2007 in Microsoft Windows 2000, XP, Vista and Windows 7 beta can handle files in different formats and converts them into other formats. It is a free software. PMID:19852806

SNP_tools: A compact tool package for analysis and conversion of genotype data for MS-Excel.

PubMed

Chen, Bowang; Wilkening, Stefan; Drechsel, Marion; Hemminki, Kari

2009-10-23

Single nucleotide polymorphism (SNP) genotyping is a major activity in biomedical research. Scientists prefer to have a facile access to the results which may require conversions between data formats. First hand SNP data is often entered in or saved in the MS-Excel format, but this software lacks genetic and epidemiological related functions. A general tool to do basic genetic and epidemiological analysis and data conversion for MS-Excel is needed. The SNP_tools package is prepared as an add-in for MS-Excel. The code is written in Visual Basic for Application, embedded in the Microsoft Office package. This add-in is an easy to use tool for users with basic computer knowledge (and requirements for basic statistical analysis). Our implementation for Microsoft Excel 2000-2007 in Microsoft Windows 2000, XP, Vista and Windows 7 beta can handle files in different formats and converts them into other formats. It is a free software.

78 FR 55752 - Center For Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

... Epidemiology Integrated Review Group, Behavioral Genetics and Epidemiology Study Section. Date: October 8, 2013... Committee: Oncology 1-Basic Translational Integrated Review Group, Cancer Genetics Study Section. Date... Biology Integrated Review Group, Molecular and Integrative Signal Transduction Study Section. Date...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinhaus, K.A.; Bennett, R.L.; Resta, R.G.

To determine consistency in usage of pedigree symbols by genetics professionals, we reviewed pedigrees printed in 10 human genetic and medical journals and 24 medical genetics textbooks. We found no consistent symbolization for common situations such as pregnancy, spontaneous abortion, death, or test results. Inconsistency in pedigree design can create difficulties in the interpretation of family studies and detract from the pedigree`s basic strength of simple and accurate communication of medical information. We recommend the development of standard pedigree symbols, and their incorporation into genetic publications, professional genetics training programs, pedigree software programs, and genetic board examinations. 5 refs., 11more » figs., 2 tabs.« less

Problem solving with genetic algorithms and Splicer

NASA Technical Reports Server (NTRS)

Bayer, Steven E.; Wang, Lui

1991-01-01

Genetic algorithms are highly parallel, adaptive search procedures (i.e., problem-solving methods) loosely based on the processes of population genetics and Darwinian survival of the fittest. Genetic algorithms have proven useful in domains where other optimization techniques perform poorly. The main purpose of the paper is to discuss a NASA-sponsored software development project to develop a general-purpose tool for using genetic algorithms. The tool, called Splicer, can be used to solve a wide variety of optimization problems and is currently available from NASA and COSMIC. This discussion is preceded by an introduction to basic genetic algorithm concepts and a discussion of genetic algorithm applications.

Paul Polani and the development of medical genetics

PubMed Central

Harper, Peter S.

2007-01-01

Paul Polani (1914-2006) was one of the key figures internationally in the beginnings and development of medical genetics. Best remembered scientifically for his highly original work on the basis of human sex chromosome disorders, notably Turner syndrome, he pioneered the application of basic biological research to clinical genetic problems. The unit that he founded in 1960, at Guys Hospital, London, provided an unparalleled model for combined research and service in medical genetics across a wide range of laboratory areas and helped to establish medical genetics as a specific discipline. PMID:17066298

Genetic testing and the future of disability insurance: ethics, law & policy.

PubMed

Wolf, Susan M; Kahn, Jeffrey P

2007-01-01

Predictive genetic testing poses fundamental questions for disability insurance, a crucial resource funding basic needs when disability prevents income from work. This article, from an NIH-funded project, presents the first indepth analysis of the challenging issues: Should disability insurers be permitted to consider genetics and exclude predicted disability? May disabilities with a recognized genetic basis be excluded from coverage as pre-existing conditions? How can we assure that private insurers writing individual and group policies, employers, and public insurers deal competently and appropriately with genetic testing?

Faculty Performance on the Genomic Nursing Concept Inventory.

PubMed

Read, Catherine Y; Ward, Linda D

2016-01-01

To use the newly developed Genomic Nursing Concept Inventory (GNCI) to evaluate faculty understanding of foundational genomic concepts, explore relative areas of strength and weakness, and compare the results with those of a student sample. An anonymous online survey instrument consisting of demographic or background items and the 31 multiple-choice questions that make up the GNCI was completed by 495 nursing faculty from across the United States in the fall of 2014. Total GNCI score and scores on four subcategories (genome basics, mutations, inheritance, genomic health) were calculated. Relationships between demographic or background variables and total GNCI score were explored. The mean score on the GNCI was 14.93 (SD = 5.31), or 48% correct; topical category scores were highest on the inheritance and genomic health items (59% and 58% correct, respectively), moderate on the mutations items (54% correct), and lowest on the genome basics items (33% correct). These results are strikingly similar to those of a recent study of nursing students. Factors associated with a higher total score on the GNCI included higher self-rated proficiency with genetic/genomic content, having a doctoral degree, having taken a genetics course for academic credit or continuing education, and having taught either a stand-alone genetic/genomic course or lecture content as part of nursing or related course. Self-rated proficiency with genetic/genomic content was fair or poor (70%), with only 7% rating their proficiency as very good or excellent. Faculty knowledge of foundational genomic concepts is similar to that of the students they teach and weakest in the areas related to basic science information. Genomics is increasingly relevant in all areas of clinical nursing practice, and the faculty charged with educating the next generation of nurses must understand foundational concepts. Faculty need to be proactive in seeking out relevant educational programs that include basic genetic/genomic concepts. © 2015 Sigma Theta Tau International.

75 FR 25273 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

... Genetics Integrated Review Group, Molecular Genetics C Study Section. Date: June 3-4, 2010. Time: 8 a.m. to... Committee: Oncology 1-Basic Translational Integrated Review Group, Cancer Molecular Pathobiology Study... Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Cellular and...

Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch

PubMed Central

Lou, Chunbo; Liu, Xili; Ni, Ming; Huang, Yiqi; Huang, Qiushi; Huang, Longwen; Jiang, Lingli; Lu, Dan; Wang, Mingcong; Liu, Chang; Chen, Daizhuo; Chen, Chongyi; Chen, Xiaoyue; Yang, Le; Ma, Haisu; Chen, Jianguo; Ouyang, Qi

2010-01-01

Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of the genetic information-processing systems. In this study, we report the design and construction of a genetic sequential logic circuit in Escherichia coli. It can generate different outputs in response to the same input signal on the basis of its internal state, and ‘memorize' the output. The circuit is composed of two parts: (1) a bistable switch memory module and (2) a double-repressed promoter NOR gate module. The two modules were individually rationally designed, and they were coupled together by fine-tuning the interconnecting parts through directed evolution. After fine-tuning, the circuit could be repeatedly, alternatively triggered by the same input signal; it functions as a push-on push-off switch. PMID:20212522

Synthesizing a novel genetic sequential logic circuit: a push-on push-off switch.

PubMed

Lou, Chunbo; Liu, Xili; Ni, Ming; Huang, Yiqi; Huang, Qiushi; Huang, Longwen; Jiang, Lingli; Lu, Dan; Wang, Mingcong; Liu, Chang; Chen, Daizhuo; Chen, Chongyi; Chen, Xiaoyue; Yang, Le; Ma, Haisu; Chen, Jianguo; Ouyang, Qi

2010-01-01

Design and synthesis of basic functional circuits are the fundamental tasks of synthetic biologists. Before it is possible to engineer higher-order genetic networks that can perform complex functions, a toolkit of basic devices must be developed. Among those devices, sequential logic circuits are expected to be the foundation of the genetic information-processing systems. In this study, we report the design and construction of a genetic sequential logic circuit in Escherichia coli. It can generate different outputs in response to the same input signal on the basis of its internal state, and 'memorize' the output. The circuit is composed of two parts: (1) a bistable switch memory module and (2) a double-repressed promoter NOR gate module. The two modules were individually rationally designed, and they were coupled together by fine-tuning the interconnecting parts through directed evolution. After fine-tuning, the circuit could be repeatedly, alternatively triggered by the same input signal; it functions as a push-on push-off switch.

Primer on Molecular Genetics; DOE Human Genome Program

DOE R&D Accomplishments Database

1992-04-01

This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

Integration of Basic Sciences in Health's Courses

ERIC Educational Resources Information Center

Azzalis, L. A.; Giavarotti, L.; Sato, S. N.; Barros, N. M. T.; Junqueira, V. B. C.; Fonseca, F. L. A.

2012-01-01

Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular Biology are essential to the understanding and treatment of an elevated number of illnesses, but often they are studied separately, with no integration between them. This article proposes a model for basic sciences integration based on problem-based learning (PBL) and…

Senior Computational Scientist | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research in basic and applied molecular biology, immunology, retrovirology, cancer biology, and human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick National Laboratory for Cancer Research (FNLCR). The Cancer & Inflammation Program (CIP),

Secretary | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research programs in basic or applied molecular biology, immunology, retrovirology, cancer biology, or human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick national Laboratory for Cancer Research (FNLCR). The BSP Office provides

Genetic factors and molecular mechanisms in dry eye disease.

PubMed

Lee, Ling; Garrett, Qian; Flanagan, Judith; Chakrabarti, Subhabrata; Papas, Eric

2018-04-01

Dry eye disease (DED) is a complex condition with a multifactorial etiology that can be difficult to manage successfully. While external factors are modifiable, treatment success is limited if genetic factors contribute to the disease. The purpose of this review is to compile research describing normal and abnormal ocular surface function on a molecular level, appraise genetic studies involving DED or DED-associated diseases, and introduce the basic methods used for conducting genetic epidemiology studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

PubMed Central

Zhang, Xiao-Hui; Tee, Louis Y; Wang, Xiao-Gang; Huang, Qun-Shan; Yang, Shi-Hua

2015-01-01

CRISPR/Cas9 is a versatile genome-editing technology that is widely used for studying the functionality of genetic elements, creating genetically modified organisms as well as preclinical research of genetic disorders. However, the high frequency of off-target activity (≥50%)—RGEN (RNA-guided endonuclease)-induced mutations at sites other than the intended on-target site—is one major concern, especially for therapeutic and clinical applications. Here, we review the basic mechanisms underlying off-target cutting in the CRISPR/Cas9 system, methods for detecting off-target mutations, and strategies for minimizing off-target cleavage. The improvement off-target specificity in the CRISPR/Cas9 system will provide solid genotype–phenotype correlations, and thus enable faithful interpretation of genome-editing data, which will certainly facilitate the basic and clinical application of this technology. PMID:26575098

Oral manifestations of hematologic and nutritional diseases.

PubMed

Schlosser, Bethanee J; Pirigyi, Megan; Mirowski, Ginat W

2011-02-01

Oral manifestations of hematologic and nutritional deficiencies can affect the mucous membranes, teeth, periodontal tissues, salivary glands, and perioral skin. This article reviews common oral manifestations of hematologic conditions starting with disorders of the white blood cells including cyclic hematopoiesis (cyclic neutropenia), leukemias, lymphomas, plasma cell dyscrasias, and mast cell disorders; this is followed by a discussion of the impact of red blood cell disorders including anemias and less common red blood cell dyscrasias (sickle cell disease, hemochromatosis, and congenital erythropoietic porphyria) as well as thrombocytopenia. Several nutritional deficiencies exhibit oral manifestations. The authors specifically discuss the impact of water-soluble vitamins (B2, B3, B6, B9, B12, and C), fat-soluble vitamins (A, D, and K) and the eating disorders anorexia nervosa and bulimia nervosa on the oral mucosa. Copyright © 2011 Elsevier Inc. All rights reserved.

Genetic data analysis for plant and animal breeding

USDA-ARS?s Scientific Manuscript database

This book is an advanced textbook covering the application of quantitative genetics theory to analysis of actual data (both trait and DNA marker information) for breeding populations of crops, trees, and animals. Chapter 1 is an introduction to basic software used for trait data analysis. Chapter 2 ...

Teaching Molecular Biology with Microcomputers.

ERIC Educational Resources Information Center

Reiss, Rebecca; Jameson, David

1984-01-01

Describes a series of computer programs that use simulation and gaming techniques to present the basic principles of the central dogma of molecular genetics, mutation, and the genetic code. A history of discoveries in molecular biology is presented and the evolution of these computer assisted instructional programs is described. (MBR)

The Five-Year Outlook on Science and Technology: 1982.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC. Committee on Science and Public Policy.

Presented are reports on trends and probable future developments in eight selected areas of basic science and engineering. These reports are: "The Genetic Program of Complex Organisms" (Maxine F. Singer); "The Molecular and Genetic Technology of Plants" (Joseph E. Varner); "Cell Receptors for Hormones and…

Sadness, Depression, and Avoidance Behavior

ERIC Educational Resources Information Center

Leventhal, Allan M.

2008-01-01

Research into genetic, psychosocial, and cognitive explanations for depression (biopsychosocial models) provides support for the role of these variables in the etiology of depression. Regularly identified as basic to depression is loss, and the experience of loss has been found to be more influential than genetic factors in the causation of…

Mechanisms, applications, and perspectives of antiviral RNA silencing in plants

PubMed Central

Garcia-Ruiz, Hernan; Ruiz, Mayra Teresa Garcia; Peralta, Sergio Manuel Gabriel; Gabriel, Cristina Betzabeth Miravel; El-Mounadi, Kautar

2017-01-01

Viral diseases of plants cause important economic losses due to reduction in crop quality and quantity to the point of threatening food security in some countries. Given the reduced availability of natural sources, genetic resistance to viruses has been successfully engineered for some plant-virus combinations. A sound understanding of the basic mechanisms governing plant-virus interactions, including antiviral RNA silencing, is the foundation to design better management strategies and biotechnological approaches to engineer and implement antiviral resistance in plants. In this review, we present current molecular models to explain antiviral RNA silencing and its application in basic plant research, biotechnology and genetic engineering. PMID:28890589

Genetics and Mathematics: Evidence from Prader-Willi Syndrome

ERIC Educational Resources Information Center

Semenza, Carlo; Pignatti, Riccardo; Bertella, Laura; Ceriani, Francesca; Mori, Ileana; Molinari, Enrico; Giardino, Daniela; Malvestiti, Francesca; Grugni, Graziano

2008-01-01

Mathematical abilities were tested in people with Prader-Willi syndrome (PWS), using a series of basic mathematical tasks for which normative data are available. The difference between the deletion and the disomy variants of this condition was explored. While a wide phenotypic variation was found, some basic findings emerge clearly. As expected…

Genetics and epidemiology, congenital anomalies and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedman, J.M.

1997-03-01

Many of the basic statistical methods used in epidemiology - regression, analysis of variance, and estimation of relative risk, for example - originally were developed for the genetic analysis of biometric data. The familiarity that many geneticists have with this methodology has helped geneticists to understand and accept genetic epidemiology as a scientific discipline. It worth noting, however, that most of the work in genetic epidemiology during the past decade has been devoted to linkage and other family studies, rather than to population-based investigations of the type that characterize much of mainstream epidemiology. 30 refs., 2 tabs.

Genetics, Environment, and Behavior: Implications for Educational Policy.

ERIC Educational Resources Information Center

Ehrman, Lee, Ed.; And Others

The contents of this book, which presents the fruits of one of a series of conferences organized by the National Research Council Committee on Basic Research in Education, includes 12 papers, with discussion and comments: "Introductory Remarks," Ernst W. Caspari; "Quantitative Aspects of Genetics and Environment in the Determination of Behavior,"…

Learning Genetics through a Scientific Inquiry Game

ERIC Educational Resources Information Center

Casanoves, Marina; Salvadó, Zoel; González, Ángel; Valls, Cristina; Novo, Maria Teresa

2017-01-01

In this paper we discuss an activity through which students learn basic concepts in genetics by taking part in a police investigation game. The activity, which we have called Recal, immerses students in a scientific-based scenario in which they play a role of a scientific assessor. Players have to develop and use scientific reasoning and…

Genetically engineered pigs as models for human disease

PubMed Central

Perleberg, Carolin; Kind, Alexander

2018-01-01

ABSTRACT Genetically modified animals are vital for gaining a proper understanding of disease mechanisms. Mice have long been the mainstay of basic research into a wide variety of diseases but are not always the most suitable means of translating basic knowledge into clinical application. The shortcomings of rodent preclinical studies are widely recognised, and regulatory agencies around the world now require preclinical trial data from nonrodent species. Pigs are well suited to biomedical research, sharing many similarities with humans, including body size, anatomical features, physiology and pathophysiology, and they already play an important role in translational studies. This role is set to increase as advanced genetic techniques simplify the generation of pigs with precisely tailored modifications designed to replicate lesions responsible for human disease. This article provides an overview of the most promising and clinically relevant genetically modified porcine models of human disease for translational biomedical research, including cardiovascular diseases, cancers, diabetes mellitus, Alzheimer's disease, cystic fibrosis and Duchenne muscular dystrophy. We briefly summarise the technologies involved and consider the future impact of recent technical advances. PMID:29419487

Electrotransformation and clonal isolation of Rickettsia species

PubMed Central

Riley, Sean P; Macaluso, Kevin R; Martinez, Juan J

2015-01-01

Genetic manipulation of obligate intracellular bacteria of the genus Rickettsia is currently undergoing a rapid period of change. The development of viable genetic tools, including replicative plasmids, transposons, homologous recombination, fluorescent protein-encoding genes, and antibiotic selectable markers has provided the impetus for future research development. This unit is designed to coalesce the basic methods pertaining to creation of genetically modified Rickettsia. The unit describes a series of methods, from inserting exogenous DNA into Rickettsia to the final isolation of genetically modified bacterial clones. Researchers working towards genetic manipulation of Rickettsia or similar obligate intracellular bacteria will find these protocols to be a valuable reference. PMID:26528784

Generation of EMS-Mutagenized Populations of Arabidopsis thaliana for Polyamine Genetics.

PubMed

Atanasov, Kostadin E; Liu, Changxin; Tiburcio, Antonio F; Alcázar, Rubén

2018-01-01

In the recent years, genetic engineering of polyamine biosynthetic genes has provided evidence for their involvement in plant stress responses and different aspects of plant development. Such approaches are being complemented with the use of reverse genetics, in which mutants affected on a particular trait, tightly associated with polyamines, are isolated and the causal genes mapped. Reverse genetics enables the identification of novel genes in the polyamine pathway, which may be involved in downstream signaling, transport, homeostasis, or perception. Here, we describe a basic protocol for the generation of ethyl methanesulfonate (EMS) mutagenized populations of Arabidopsis thaliana for its use in reverse genetics applied to polyamines.

Ciona Genetics

PubMed Central

Veeman, Michael T.; Chiba, Shota; Smith, William C.

2010-01-01

Ascidians, such as Ciona, are invertebrate chordates with simple embryonic body plans and small, relatively non-redundant genomes. Ciona genetics is in its infancy compared to many other model systems, but it provides a powerful method for studying this important vertebrate outgroup. Here we give basic methods for genetic analysis of Ciona, including protocols for controlled crosses both by natural spawning and by the surgical isolation of gametes; the identification and propagation of mutant lines; and strategies for positional cloning. PMID:21805273

Genetic dissection of growth, wood basic density and gene expression in interspecific backcrosses of Eucalyptus grandis and E. urophylla

PubMed Central

2012-01-01

Background F1 hybrid clones of Eucalyptus grandis and E. urophylla are widely grown for pulp and paper production in tropical and subtropical regions. Volume growth and wood quality are priority objectives in Eucalyptus tree improvement. The molecular basis of quantitative variation and trait expression in eucalypt hybrids, however, remains largely unknown. The recent availability of a draft genome sequence (http://www.phytozome.net) and genome-wide genotyping platforms, combined with high levels of genetic variation and high linkage disequilibrium in hybrid crosses, greatly facilitate the detection of quantitative trait loci (QTLs) as well as underlying candidate genes for growth and wood property traits. In this study, we used Diversity Arrays Technology markers to assess the genetic architecture of volume growth (diameter at breast height, DBH) and wood basic density in four-year-old progeny of an interspecific backcross pedigree of E. grandis and E. urophylla. In addition, we used Illumina RNA-Seq expression profiling in the E. urophylla backcross family to identify cis- and trans-acting polymorphisms (eQTLs) affecting transcript abundance of genes underlying QTLs for wood basic density. Results A total of five QTLs for DBH and 12 for wood basic density were identified in the two backcross families. Individual QTLs for DBH and wood basic density explained 3.1 to 12.2% of phenotypic variation. Candidate genes underlying QTLs for wood basic density on linkage groups 8 and 9 were found to share trans-acting eQTLs located on linkage groups 4 and 10, which in turn coincided with QTLs for wood basic density suggesting that these QTLs represent segregating components of an underlying transcriptional network. Conclusion This is the first demonstration of the use of next-generation expression profiling to quantify transcript abundance in a segregating tree population and identify candidate genes potentially affecting wood property variation. The QTLs identified in this study provide a resource for identifying candidate genes and developing molecular markers for marker-assisted breeding of volume growth and wood basic density. Our results suggest that integrated analysis of transcript and trait variation in eucalypt hybrids can be used to dissect the molecular basis of quantitative variation in wood property traits. PMID:22817272

An integrated biochemistry and genetics outreach program designed for elementary school students.

PubMed

Ross, Eric D; Lee, Sarah K; Radebaugh, Catherine A; Stargell, Laurie A

2012-02-01

Exposure to genetic and biochemical experiments typically occurs late in one's academic career. By the time students have the opportunity to select specialized courses in these areas, many have already developed negative attitudes toward the sciences. Given little or no direct experience with the fields of genetics and biochemistry, it is likely that many young people rule these out as potential areas of study or career path. To address this problem, we developed a 7-week (~1 hr/week) hands-on course to introduce fifth grade students to basic concepts in genetics and biochemistry. These young students performed a series of investigations (ranging from examining phenotypic variation, in vitro enzymatic assays, and yeast genetic experiments) to explore scientific reasoning through direct experimentation. Despite the challenging material, the vast majority of students successfully completed each experiment, and most students reported that the experience increased their interest in science. Additionally, the experiments within the 7-week program are easily performed by instructors with basic skills in biological sciences. As such, this program can be implemented by others motivated to achieve a broader impact by increasing the accessibility of their university and communicating to a young audience a positive impression of the sciences and the potential for science as a career.

Establishment of the Fox Chase Network Breast Cancer Risk Registry.

DTIC Science & Technology

1998-10-01

urologists, pathologists, nurses, health educators, genetic counselors, epidemiologists, behavioral scientists, nutritionists and basic scientists. The...data can readily be translated into a family pedigree for counseling and teaching purposes. Our success in confirming diagnoses with medical records...didactic and interactive teaching covering the following topics: fundamentals of cancer genetics; cancer inheritance patterns; risk assessment and

"Sickle Cell Anemia: Tracking down a Mutation": An Interactive Learning Laboratory That Communicates Basic Principles of Genetics and Cellular Biology

ERIC Educational Resources Information Center

Jarrett, Kevin; Williams, Mary; Horn, Spencer; Radford, David; Wyss, J. Michael

2016-01-01

"Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients…

Phytophthora ramorum and sudden oak death in California: III. preliminary studies in pathogen genetics

Treesearch

Matteo Garbelotto; David M. Rizzo; Katie Hayden; Monica Meija-Chang; Jennifer M. Davidson; Steven Tjosvold

2002-01-01

Sudden oak death (SOD) has been shown to be caused by a new species of Phytophthora, P. ramorum. A basic understanding of the genetics of P. ramorum is critical to any management strategy. We have initiated a number of studies to examine species concepts, population biology and mating behavior of the pathogen....

Genetic literacy series: Primer part 2-Paradigm shifts in epilepsy genetics.

PubMed

Helbig, Ingo; Heinzen, Erin L; Mefford, Heather C

2018-05-09

This is the second of a 2-part primer on the genetics of the epilepsies within the Genetic Literacy Series of the Genetics Commission of the International League Against Epilepsy. In Part 1, we covered types of genetic variation, inheritance patterns, and their relationship to disease. In Part 2, we apply these basic principles to the case of a young boy with epileptic encephalopathy and ask 3 important questions: (1) Is the gene in question an established genetic etiology for epilepsy? (2) Is the variant in this particular gene pathogenic by established variant interpretation criteria? (3) Is the variant considered causative in the clinical context? These questions are considered and then answered for the clinical case in question. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

The biology of cancer: what do oncology nurses really need to know.

PubMed

Eggert, Julie

2011-02-01

To describe the impact of genetics and genomics on the biology of cancer and the implications for patient care. Pubmed; CINAHL. Cancer research in genetics/genomics has identified new mechanisms influencing personalized risk assessment/management, early detection, cancer treatment, and long-term screening/surveillance. Understanding the basics of genetics/genomics on the biology of cancer will facilitate patient education and care delivery, including the administration and monitoring of genetically targeted therapies whose toxicities may in part be mediated by the molecular pathways targeted by the specific agent. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular epidemiology of clonal diploids: a quick overview and a short DIY (do it yourself) notice.

PubMed

De Meeûs, Thierry; Lehmann, Laurent; Balloux, François

2006-03-01

In this short review we report the basic notions needed for understanding the population genetics of clonal diploids. We focus on the consequences of clonality on the distribution of genetic diversity within individuals, between individuals and between populations. We then summarise how to detect clonality in mainly sexual populations, conversely, how to detect sexuality in mainly clonal populations and also how genetic differentiation between populations is affected by clonality in diploids. This information is then used for building recipes on how to analyse and interpret genetic polymorphism data in molecular epidemiology studies of clonal diploids.

Resolving the evolutionary paradox of genetic instability: a cost-benefit analysis of DNA repair in changing environments.

PubMed

Breivik, Jarle; Gaudernack, Gustav

2004-04-09

Loss of genetic stability is a critical phenomenon in cancer and antibiotic resistance, and the prevailing dogma is that unstable cells survive because instability provides adaptive mutations. Challenging this view, we have argued that genetic instability arises because DNA repair may be a counterproductive strategy in mutagenic environments. This paradoxical relationship has also been confirmed by explicit experiments, but the underlying evolutionary principles remain controversial. This paper aims to clarify the issue, and presents a model that explains genetic instability from the basic perspective of molecular evolution and information processing.

Molecular genetics made simple

PubMed Central

Kassem, Heba Sh.; Girolami, Francesca; Sanoudou, Despina

2012-01-01

Abstract Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients. PMID:25610837

In this issue: from basic immunology to oncogenesis and inflammation.

PubMed

Bot, Adrian

2013-06-01

This issue of the International Reviews of Immunology features very diverse topics from basic immunology to inflammation, oncogenesis and immunopathology. Specifically, this volume hosts reviews describing the role of TCRγδ T cells, the significance of Epstein Barr virus-associated miRNAs and the genetic basis of Hashimoto's thyroiditis along with other reviews on the topics mentioned above.

Selfish genetic elements, genetic conflict, and evolutionary innovation.

PubMed

Werren, John H

2011-06-28

Genomes are vulnerable to selfish genetic elements (SGEs), which enhance their own transmission relative to the rest of an individual's genome but are neutral or harmful to the individual as a whole. As a result, genetic conflict occurs between SGEs and other genetic elements in the genome. There is growing evidence that SGEs, and the resulting genetic conflict, are an important motor for evolutionary change and innovation. In this review, the kinds of SGEs and their evolutionary consequences are described, including how these elements shape basic biological features, such as genome structure and gene regulation, evolution of new genes, origin of new species, and mechanisms of sex determination and development. The dynamics of SGEs are also considered, including possible "evolutionary functions" of SGEs.

Selfish genetic elements, genetic conflict, and evolutionary innovation

PubMed Central

Werren, John H.

2011-01-01

Genomes are vulnerable to selfish genetic elements (SGEs), which enhance their own transmission relative to the rest of an individual's genome but are neutral or harmful to the individual as a whole. As a result, genetic conflict occurs between SGEs and other genetic elements in the genome. There is growing evidence that SGEs, and the resulting genetic conflict, are an important motor for evolutionary change and innovation. In this review, the kinds of SGEs and their evolutionary consequences are described, including how these elements shape basic biological features, such as genome structure and gene regulation, evolution of new genes, origin of new species, and mechanisms of sex determination and development. The dynamics of SGEs are also considered, including possible “evolutionary functions” of SGEs. PMID:21690392

The various aspects of genetic and epigenetic toxicology: testing methods and clinical applications.

PubMed

Ren, Ning; Atyah, Manar; Chen, Wan-Yong; Zhou, Chen-Hao

2017-05-22

Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells.

Genetic perspectives on northern population cycles: bridging the gap between theory and empirical studies.

PubMed

Norén, Karin; Angerbjörn, Anders

2014-05-01

Many key species in northern ecosystems are characterised by high-amplitude cyclic population demography. In 1924, Charles Elton described the ecology and evolution of cyclic populations in a classic paper and, since then, a major focus has been the underlying causes of population cycles. Elton hypothesised that fluctuations reduced population genetic variation and influenced the direction of selection pressures. In concordance with Elton, present theories concern the direct consequences of population cycles for genetic structure due to the processes of genetic drift and selection, but also include feedback models of genetic composition on population dynamics. Most of these theories gained mathematical support during the 1970s and onwards, but due to methodological drawbacks, difficulties in long-term sampling and a complex interplay between microevolutionary processes, clear empirical data allowing the testing of these predictions are still scarce. Current genetic tools allow for estimates of genetic variation and identification of adaptive genomic regions, making this an ideal time to revisit this subject. Herein, we attempt to contribute towards a consensus regarding the enigma described by Elton almost 90 years ago. We present nine predictions covering the direct and genetic feedback consequences of population cycles on genetic variation and population structure, and review the empirical evidence. Generally, empirical support for the predictions was low and scattered, with obvious gaps in the understanding of basic population processes. We conclude that genetic variation in northern cyclic populations generally is high and that the geographic distribution and amount of diversity are usually suggested to be determined by various forms of context- and density-dependent dispersal exceeding the impact of genetic drift. Furthermore, we found few clear signatures of selection determining genetic composition in cyclic populations. Dispersal is assumed to have a strong impact on genetic structuring and we suggest that the signatures of other microevolutionary processes such as genetic drift and selection are weaker and have been over-shadowed by density-dependent dispersal. We emphasise that basic biological and demographical questions still need to be answered and stress the importance of extensive sampling, appropriate choice of tools and the value of standardised protocols. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

Institutional Profile: University of Chicago Center for Personalized Therapeutics: research, education and implementation science.

PubMed

Dolan, M Eileen; Maitland, Michael L; O'Donnell, Peter H; Nakamura, Yusuke; Cox, Nancy J; Ratain, Mark J

2013-09-01

Pharmacogenomics is aimed at advancing our knowledge of the genetic basis of variable drug response. The Center for Personalized Therapeutics within the University of Chicago comprises basic, translational and clinical research as well as education including undergraduate, graduate, medical students, clinical/postdoctoral fellows and faculty. The Committee on Clinical Pharmacology and Pharmacogenomics is the educational arm of the Center aimed at training clinical and postdoctoral fellows in translational pharmacology and pharmacogenomics. Research runs the gamut from basic discovery and functional studies to pharmacogenomic implementation studies to evaluate physician adoption of genetic medicine. The mission of the Center is to facilitate research, education and implementation of pharmacogenomics to realize the true potential of personalized medicine and improve the lives of patients.

Editorial overview: Molecular and genetic bases of disease: the double life of DNA.

PubMed

McMurray, Cynthia T; Vijg, Jan

2014-06-01

This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest with the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA guide both the transitions to life as well as the transitions to death. Published by Elsevier Ltd.

The adequacy of informed consent forms in genetic research in Oman: a pilot study.

PubMed

Al-Riyami, Asya; Jaju, Deepali; Jaju, Sanjay; Silverman, Henry J

2011-08-01

Genetic research presents ethical challenges to the achievement of valid informed consent, especially in developing countries with areas of low literacy. During the last several years, a number of genetic research proposals involving Omani nationals were submitted to the Department of Research and Studies, Ministry of Health, Oman. The objective of this paper is to report on the results of an internal quality assurance initiative to determine the extent of the information being provided in genetic research informed consent forms. In order to achieve this, we developed checklists to assess the inclusion of basic elements of informed consent as well as elements related to the collection and future storage of biological samples. Three of the authors independently evaluated and reached consensus on seven informed consent forms that were available for review. Of the seven consent forms, four had less than half of the basic elements of informed consent. None contained any information regarding whether genetic information relevant to health would be disclosed, whether participants may share in commercial products, the extent of confidentiality protections, and the inclusion of additional consent forms for future storage and use of tissue samples. Information regarding genetic risks and withdrawal of samples were rarely mentioned (1/7), whereas limits on future use of samples were mentioned in 3 of 7 consent forms. Ultimately, consent forms are not likely to address key issues regarding genetic research that have been recommended by research ethics guidelines. We recommend enhanced educational efforts to increase awareness, on the part of researchers, of information that should be included in consent forms. © 2011 Blackwell Publishing Ltd.

Forest genetics research at the University of Michigan

Treesearch

Burton V. Barnes

1970-01-01

The purpose of the research program, as evidenced by results as well as current research and future direction, is to add to the knowledge of the ecology and genetics of forest trees. Although we are interested in the practical gains that are possible and being realized in practical tree improvement, our contribution is in basic studies that stimulate and challenge...

Prediction/Discussion-Based Learning Cycle versus Conceptual Change Text: Comparative Effects on Students' Understanding of Genetics

ERIC Educational Resources Information Center

Al khawaldeh, Salem A.

2013-01-01

Background and Purpose: The purpose of this study was to investigate the comparative effects of a prediction/discussion-based learning cycle (HPD-LC), conceptual change text (CCT) and traditional instruction on 10th grade students' understanding of genetics concepts. Sample: Participants were 112 10th basic grade male students in three classes of…

77 FR 56855 - Center For Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-14

... Review Group; Molecular Genetics A Study Section. Date: October 15-16, 2012. Time: 8:00 a.m. to 6:00 p.m... Genetics Study Section. Date: October 15, 2012. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and evaluate...: Oncology 1--Basic Translational Integrated Review Group; Cancer Molecular Pathobiology Study Section. Date...

“Sickle cell anemia: tracking down a mutation”: an interactive learning laboratory that communicates basic principles of genetics and cellular biology

PubMed Central

Jarrett, Kevin; Williams, Mary; Horn, Spencer; Radford, David

2016-01-01

“Sickle cell anemia: tracking down a mutation” is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients have the sickle cell genotype/phenotype using DNA and blood samples from wild-type and transgenic mice that carry a sickle cell mutation. The inquiry-based, problem-solving approach facilitates the students' understanding of the basic concepts of genetics and cellular and molecular biology and provides experience with contemporary tools of biotechnology. It also leads to students' appreciation of the causes and consequences of this genetic disease, which is relatively common in individuals of African descent, and increases their understanding of the first principles of genetics. This protocol provides optimal learning when led by well-trained facilitators (including the classroom teacher) and carried out in small groups (6:1 student-to-teacher ratio). This high-quality experience can be offered to a large number of students at a relatively low cost, and it is especially effective in collaboration with a local science museum and/or university. Over the past 15 yr, >12,000 students have completed this inquiry-based learning experience and demonstrated a consistent, substantial increase in their understanding of the disease and genetics in general. PMID:26873898

"Sickle cell anemia: tracking down a mutation": an interactive learning laboratory that communicates basic principles of genetics and cellular biology.

PubMed

Jarrett, Kevin; Williams, Mary; Horn, Spencer; Radford, David; Wyss, J Michael

2016-03-01

"Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients have the sickle cell genotype/phenotype using DNA and blood samples from wild-type and transgenic mice that carry a sickle cell mutation. The inquiry-based, problem-solving approach facilitates the students' understanding of the basic concepts of genetics and cellular and molecular biology and provides experience with contemporary tools of biotechnology. It also leads to students' appreciation of the causes and consequences of this genetic disease, which is relatively common in individuals of African descent, and increases their understanding of the first principles of genetics. This protocol provides optimal learning when led by well-trained facilitators (including the classroom teacher) and carried out in small groups (6:1 student-to-teacher ratio). This high-quality experience can be offered to a large number of students at a relatively low cost, and it is especially effective in collaboration with a local science museum and/or university. Over the past 15 yr, >12,000 students have completed this inquiry-based learning experience and demonstrated a consistent, substantial increase in their understanding of the disease and genetics in general. Copyright © 2016 The American Physiological Society.

Genetic variation in basic density and modulus of elasticity of coastal Douglas-fir.

Treesearch

G.R. Johnson; B.L. Gartner

2006-01-01

Douglas-fir trees from 39 open-pollinated families at four test locations were assessed to estimate heritability of modulus of elasticity (MOE) and basic density. Heritability estimates of MOE (across-site h = 0.55) were larger than those for total height (0.15) and diameter at breast height (DBH; 0.29), and similar to those for density (0.59)....

Immunogenetics of the Elephant Seal

NASA Technical Reports Server (NTRS)

Garza, John Carlos

1999-01-01

The goals of this cooperative agreement fall into three categories: 1) A basic description of Immunogenetic variation in the northern elephant seal genome; 2) A basic genetic map of the northern elephant seal genome; 3). Microevolutionary forces in the northern elephant seal genome. The results described in this report were acquired using funds from this cooperative agreement together with funds from a National Science Foundation Dissertation Improvement Grant.

Publishing a master's thesis: a guide for novice authors.

PubMed

Resta, Robert G; McCarthy Veach, Patricia; Charles, Sarah; Vogel, Kristen; Blase, Terri; Palmer, Christina G S

2010-06-01

Publication of original research, clinical experiences, and critical reviews of literature are vital to the growth of the genetic counseling field, delivery of genetic counseling services, and professional development of genetic counselors. Busy clinical schedules, lack of time and funding, and training that emphasizes clinical skills over research skills may make it difficult for new genetic counselors to turn their thesis projects into publications. This paper summarizes and elaborates upon a presentation aimed at de-mystifying the publishing process given at the 2008 National Society of Genetic Counselors Annual Education Conference. Specific topics include familiarizing prospective authors, particularly genetic counseling students, with the basics of the publication process and related ethical considerations. Former students' experiences with publishing master's theses also are described in hopes of encouraging new genetic counselors to submit for publication papers based on their thesis projects.

Getting a head start: the importance of personal genetics education in high schools.

PubMed

Kung, Johnny T; Gelbart, Marnie E

2012-03-01

With advances in sequencing technology, widespread and affordable genome sequencing will soon be a reality. However, studies suggest that "genetic literacy" of the general public is inadequate to prepare our society for this unprecedented access to our genetic information. As the current generation of high school students will come of age in an era when personal genetic information is increasingly utilized in health care, it is of vital importance to ensure these students understand the genetic concepts necessary to make informed medical decisions. These concepts include not only basic scientific knowledge, but also considerations of the ethical, legal, and social issues that will arise in the age of personal genomics. In this article, we review the current state of genetics education, highlight issues that we believe need to be addressed in a comprehensive genetics education curriculum, and describe our education efforts at the Harvard Medical School-based Personal Genetics Education Project.

The complete nucleotide sequences of the 5 genetically distinct plastid genomes of Oenothera, subsection Oenothera: II. A microevolutionary view using bioinformatics and formal genetic data.

PubMed

Greiner, Stephan; Wang, Xi; Herrmann, Reinhold G; Rauwolf, Uwe; Mayer, Klaus; Haberer, Georg; Meurer, Jörg

2008-09-01

A unique combination of genetic features and a rich stock of information make the flowering plant genus Oenothera an appealing model to explore the molecular basis of speciation processes including nucleus-organelle coevolution. From representative species, we have recently reported complete nucleotide sequences of the 5 basic and genetically distinguishable plastid chromosomes of subsection Oenothera (I-V). In nature, Oenothera plastid genomes are associated with 6 distinct, either homozygous or heterozygous, diploid nuclear genotypes of the 3 basic genomes A, B, or C. Artificially produced plastome-genome combinations that do not occur naturally often display interspecific plastome-genome incompatibility (PGI). In this study, we compare formal genetic data available from all 30 plastome-genome combinations with sequence differences between the plastomes to uncover potential determinants for interspecific PGI. Consistent with an active role in speciation, a remarkable number of genes have high Ka/Ks ratios. Different from the Solanacean cybrid model Atropa/tobacco, RNA editing seems not to be relevant for PGIs in Oenothera. However, predominantly sequence polymorphisms in intergenic segments are proposed as possible sources for PGI. A single locus, the bidirectional promoter region between psbB and clpP, is suggested to contribute to compartmental PGI in the interspecific AB hybrid containing plastome I (AB-I), consistent with its perturbed photosystem II activity.

Physics for excited neutrons

NASA Astrophysics Data System (ADS)

Cartlidge, Edwin

2017-01-01

Some scientists claim they can control genetically engineered neurons using magnetic fields. Have they and the high-profile journals that published their research failed to understand basic physics? Edwin Cartlidge investigates

Lab to farm: applying research on plant genetics and genomics to crop improvement.

PubMed

Ronald, Pamela C

2014-06-01

Over the last 300 years, plant science research has provided important knowledge and technologies for advancing the sustainability of agriculture. In this Essay, I describe how basic research advances have been translated into crop improvement, explore some lessons learned, and discuss the potential for current and future contribution of plant genetic improvement technologies to continue to enhance food security and agricultural sustainability.

Controlling complexity: the clinical relevance of mouse complex genetics

PubMed Central

Schughart, Klaus; Libert, Claude; Kas, Martien J

2013-01-01

Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches. PMID:23632795

American chestnut: A test case for genetic engineering?

Treesearch

Leila Pinchot

2014-01-01

The thought of genetically engineered (GE) trees might conjure images of mutant trees with unnatural and invasive tendencies, but there is much more to the story. GE trees are a new reality that, like it or not, will probably be part of the future of forestry. The basic inclination of most Forest Guild stewards is to reject GE trees as violating our principle to...

A formulation of the foundations of genetics and evolution.

PubMed

Bahr, Brian Edward

2016-05-01

This paper proposes a formulation of theories of the foundations of genetics and evolution that can be used to mathematically simulate phenotype expression, reproduction, mutation, and natural selection. It will be shown that Mendelian inheritance can be mathematically simulated with expressions involving matrices and that these expressions can also simulate phenomena that are modifications to Mendel's basic principles, like alleles that give rise to quantitative effects and traits that are the expression of multiple alleles and/or multiple genetic loci. Copyright © 2016 Elsevier Inc. All rights reserved.

Publishing a Master’s Thesis: A Guide for Novice Authors

PubMed Central

Resta, Robert G.; McCarthy Veach, Patricia; Charles, Sarah; Vogel, Kristen; Blase, Terri

2010-01-01

Publication of original research, clinical experiences, and critical reviews of literature are vital to the growth of the genetic counseling field, delivery of genetic counseling services, and professional development of genetic counselors. Busy clinical schedules, lack of time and funding, and training that emphasizes clinical skills over research skills may make it difficult for new genetic counselors to turn their thesis projects into publications. This paper summarizes and elaborates upon a presentation aimed at de-mystifying the publishing process given at the 2008 National Society of Genetic Counselors Annual Education Conference. Specific topics include familiarizing prospective authors, particularly genetic counseling students, with the basics of the publication process and related ethical considerations. Former students’ experiences with publishing master’s theses also are described in hopes of encouraging new genetic counselors to submit for publication papers based on their thesis projects. PMID:20076994

RNAi in Arthropods: Insight into the Machinery and Applications for Understanding the Pathogen-Vector Interface

PubMed Central

Barnard, Annette-Christi; Nijhof, Ard M.; Fick, Wilma; Stutzer, Christian; Maritz-Olivier, Christine

2012-01-01

The availability of genome sequencing data in combination with knowledge of expressed genes via transcriptome and proteome data has greatly advanced our understanding of arthropod vectors of disease. Not only have we gained insight into vector biology, but also into their respective vector-pathogen interactions. By combining the strengths of postgenomic databases and reverse genetic approaches such as RNAi, the numbers of available drug and vaccine targets, as well as number of transgenes for subsequent transgenic or paratransgenic approaches, have expanded. These are now paving the way for in-field control strategies of vectors and their pathogens. Basic scientific questions, such as understanding the basic components of the vector RNAi machinery, is vital, as this allows for the transfer of basic RNAi machinery components into RNAi-deficient vectors, thereby expanding the genetic toolbox of these RNAi-deficient vectors and pathogens. In this review, we focus on the current knowledge of arthropod vector RNAi machinery and the impact of RNAi on understanding vector biology and vector-pathogen interactions for which vector genomic data is available on VectorBase. PMID:24705082

Dual-objective optimization of organic Rankine cycle (ORC) systems using genetic algorithm: a comparison between basic and recuperative cycles

NASA Astrophysics Data System (ADS)

Hayat, Nasir; Ameen, Muhammad Tahir; Tariq, Muhammad Kashif; Shah, Syed Nadeem Abbas; Naveed, Ahmad

2017-08-01

Exploitation of low potential waste thermal energy for useful net power output can be done by manipulating organic Rankine cycle systems. In the current article dual-objectives (η_{th} and SIC) optimization of ORC systems [basic organic Rankine cycle (BORC) and recuperative organic Rankine cycle (RORC)] has been done using non-dominated sorting genetic algorithm (II). Seven organic compounds (R-123, R-1234ze, R-152a, R-21, R-236ea, R-245ca and R-601) have been employed in basic cycle and four dry compounds (R-123, R-236ea, R-245ca and R-601) have been employed in recuperative cycle to investigate the behaviour of two systems and compare their performance. Sensitivity analyses show that recuperation boosts the thermodynamic behaviour of systems but it also raises specific investment cost significantly. R-21, R-245ca and R-601 show attractive performance in BORC whereas R-601 and R-236ea in RORC. RORC, due to higher total investment cost and operation & maintenance costs, has longer payback periods as compared to BORC.

Catastrophic childhood epilepsy: a recent convergence of basic and clinical neuroscience.

PubMed

Katsnelson, Alla; Buzsáki, Gyorgy; Swann, John W

2014-11-12

Advances in understanding the genetics and underlying pathology of the catastrophic childhood epilepsies are pointing toward treatments. Copyright © 2014, American Association for the Advancement of Science.

Environmental isolation explains Iberian genetic diversity in the highly homozygous model grass Brachypodium distachyon.

PubMed

Marques, Isabel; Shiposha, Valeriia; López-Alvarez, Diana; Manzaneda, Antonio J; Hernandez, Pilar; Olonova, Marina; Catalán, Pilar

2017-06-15

Brachypodium distachyon (Poaceae), an annual Mediterranean Aluminum (Al)-sensitive grass, is currently being used as a model species to provide new information on cereals and biofuel crops. The plant has a short life cycle and one of the smallest genomes in the grasses being well suited to experimental manipulation. Its genome has been fully sequenced and several genomic resources are being developed to elucidate key traits and gene functions. A reliable germplasm collection that reflects the natural diversity of this species is therefore needed for all these genomic resources. However, despite being a model plant, we still know very little about its genetic diversity. As a first step to overcome this gap, we used nuclear Simple Sequence Repeats (nSSR) to study the patterns of genetic diversity and population structure of B. distachyon in 14 populations sampled across the Iberian Peninsula (Spain), one of its best known areas. We found very low levels of genetic diversity, allelic number and heterozygosity in B. distachyon, congruent with a highly selfing system. Our results indicate the existence of at least three genetic clusters providing additional evidence for the existence of a significant genetic structure in the Iberian Peninsula and supporting this geographical area as an important genetic reservoir. Several hotspots of genetic diversity were detected and populations growing on basic soils were significantly more diverse than those growing in acidic soils. A partial Mantel test confirmed a statistically significant Isolation-By-Distance (IBD) among all studied populations, as well as a statistically significant Isolation-By-Environment (IBE) revealing the presence of environmental-driven isolation as one explanation for the genetic patterns found in the Iberian Peninsula. The finding of higher genetic diversity in eastern Iberian populations occurring in basic soils suggests that these populations can be better adapted than those occurring in western areas of the Iberian Peninsula where the soils are more acidic and accumulate toxic Al ions. This suggests that the western Iberian acidic soils might prevent the establishment of Al-sensitive B. distachyon populations, potentially causing the existence of more genetically depauperated individuals.

Novel Genetic Tools to Accelerate Our Understanding of Photosynthesis and Lipid Accumulation

DTIC Science & Technology

2014-08-20

understanding of photosynthesis and lipid accumulation Martin C. Jonikas, Ph.D. Carnegie Institution for Science, Department of Plant Biology 260...knowledge of algal lipid metabolism and photosynthesis . Advances in our basic understanding of these processes will facilitate genetic engineering of...algae to improve lipid yields. Currently, one of the greatest roadblocks in the study of algal photosynthesis and lipid metabolism is the slow pace of

Lab to Farm: Applying Research on Plant Genetics and Genomics to Crop Improvement

PubMed Central

Ronald, Pamela C.

2014-01-01

Over the last 300 years, plant science research has provided important knowledge and technologies for advancing the sustainability of agriculture. In this Essay, I describe how basic research advances have been translated into crop improvement, explore some lessons learned, and discuss the potential for current and future contribution of plant genetic improvement technologies to continue to enhance food security and agricultural sustainability. PMID:24915201

Promoting Self-Directed Learning in Developing or Poorly Defined Subject Areas: A Problem-Based Course in Molecular Biology, Genetics, and Cancer.

ERIC Educational Resources Information Center

Edmondson, Katherine M.

A new problem-based course in molecular biology, genetics, and cancer for first-year veterinary students was developed at the College of Veterinary Medicine at Cornell University (New York). The course was developed out of a desire to foster student-centered and lifelong learning and to integrate basic and clinical science knowledge despite a lack…

Regulation of TCR Signaling to NF-kB

DTIC Science & Technology

2013-03-20

applications and benefits to basic research are discussed in detail in Chapter 4.      16   CHAPTER 2: Selective autophagy of the...To confirm the specificity of the chemical inhibitors of autophagy, we employed a genetic approach. Specifically, we in vitro differentiated Th2...MG132 treatment. These data provide strong genetic evidence that TCR-mediated degradation of endogenous Bcl10 is controlled by autophagy, with a

Proceedings from the 2009 Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back

PubMed Central

Rauen, Katherine A.; Schoyer, Lisa; McCormick, Frank; Lin, Angela E.; Allanson, Judith E.; Stevenson, David A.; Gripp, Karen W.; Neri, Giovanni; Carey, John C.; Legius, Eric; Tartaglia, Marco; Schubbert, Suzanne; Roberts, Amy E.; Gelb, Bruce D.; Shannon, Kevin; Gutmann, David H.; McMahon, Martin; Guerra, Carmen; Fagin, James A.; Yu, Benjamin; Aoki, Yoko; Neel, Ben G.; Balmain, Allan; Drake, Richard R.; Nolan, Garry P.; Zenker, Martin; Bollag, Gideon; Sebolt-Leopold, Judith; Gibbs, Jackson B.; Silva, Alcino J.; Patton, E. Elizabeth; Viskochil, David H.; Kieran, Mark W.; Korf, Bruce R.; Hagerman, Randi J.; Packer, Roger J.; Melese, Teri

2012-01-01

The RASopathies are a group of genetic syndromes caused by germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Some of these syndromes are neurofibromatosis type 1, Noonan syndrome, Costello syndrome, cardio-facio-cutaneous syndrome, LEOPARD syndrome and Legius syndrome. Their common underlying pathogenetic mechanism brings about significant overlap in phenotypic features and includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The proceedings from the symposium “Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back” chronicle the timely and typical research symposium which brought together clinicians, basic scientists, physician-scientists, advocate leaders, trainees, students and individuals with Ras syndromes and their families. The goals, to discuss basic science and clinical issues, to set forth a solid framework for future research, to direct translational applications towards therapy and to set forth best practices for individuals with RASopathies was successfully meet with a commitment to begin to move towards clinical trials. PMID:20014119

"What is this genetics, anyway?" Understandings of genetics, illness causality and inheritance among British Pakistani users of genetic services.

PubMed

Shaw, Alison; Hurst, Jane A

2008-08-01

Misconceptions about basic genetic concepts and inheritance patterns may be widespread in the general population. This paper investigates understandings of genetics, illness causality and inheritance among British Pakistanis referred to a UK genetics clinic. During participant observation of genetics clinic consultations and semi-structured interviews in Urdu or English in respondents' homes, we identified an array of environmental, behavioral and spiritual understandings of the causes of medical and intellectual problems. Misconceptions about the location of genetic information in the body and of genetic mechanisms of inheritance were common, reflected the range of everyday theories observed for White British patients and included the belief that a child receives more genetic material from the father than the mother. Despite some participants' conversational use of genetic terminology, some patients had assimilated genetic information in ways that conflict with genetic theory with potentially serious clinical consequences. Additionally, skepticism of genetic theories of illness reflected a rejection of a dominant discourse of genetic risk that stigmatizes cousin marriages. Patients referred to genetics clinics may not easily surrender their lay or personal theories about the causes of their own or their child's condition and their understandings of genetic risk. Genetic counselors may need to identify, work with and at times challenge patients' understandings of illness causality and inheritance.

A Genetic Algorithm Tool (splicer) for Complex Scheduling Problems and the Space Station Freedom Resupply Problem

NASA Technical Reports Server (NTRS)

Wang, Lui; Valenzuela-Rendon, Manuel

1993-01-01

The Space Station Freedom will require the supply of items in a regular fashion. A schedule for the delivery of these items is not easy to design due to the large span of time involved and the possibility of cancellations and changes in shuttle flights. This paper presents the basic concepts of a genetic algorithm model, and also presents the results of an effort to apply genetic algorithms to the design of propellant resupply schedules. As part of this effort, a simple simulator and an encoding by which a genetic algorithm can find near optimal schedules have been developed. Additionally, this paper proposes ways in which robust schedules, i.e., schedules that can tolerate small changes, can be found using genetic algorithms.

Genetics of Movement Disorders and the Practicing Clinician; Who and What to Test for?

PubMed

Di Fonzo, Alessio; Monfrini, Edoardo; Erro, Roberto

2018-05-23

This review aims to provide the basic knowledge on the genetics of hypokinetic and hyperkinetic movement disorders to guide clinicians in the decision of "who and what to test for?" In recent years, the identification of various genetic causes of hypokinetic and hyperkinetic movement disorders has had a great impact on a better definition of different clinical syndromes. Indeed, the advent of next-generation sequencing (NGS) techniques has provided an impressive step forward in the easy identification of genetic forms. However, this increased availability of genetic testing has challenges, including the ethical issue of genetic testing in unaffected family members, "commercially" available home testing kits and the increasing number and relevance of "variants of unknown significance." The emergent role of genetic factors has important implications on clinical practice and counseling. As a consequence, it is fundamental that practicing neurologists have a proper knowledge of the genetic background of the diseases and perform an accurate selection of who has to be tested and for which gene mutations.

HFE gene in primary and secondary hepatic iron overload

PubMed Central

Sebastiani, Giada; Walker, Ann P

2007-01-01

Distinct from hereditary haemochromatosis, hepatic iron overload is a common finding in several chronic liver diseases. Many studies have investigated the prevalence, distribution and possible contributory role of excess hepatic iron in non-haemochromatotic chronic liver diseases. Indeed, some authors have proposed iron removal in liver diseases other than hereditary haemochromatosis. However, the pathogenesis of secondary iron overload remains unclear. The High Fe (HFE) gene has been implicated, but the reported data are controversial. In this article, we summarise current concepts regarding the cellular role of the HFE protein in iron homeostasis. We review the current status of the literature regarding the prevalence, hepatic distribution and possible therapeutic implications of iron overload in chronic hepatitis C, hepatitis B, alcoholic and non-alcoholic fatty liver diseases and porphyria cutanea tarda. We discuss the evidence regarding the role of HFE gene mutations in these liver diseases. Finally, we summarize the common and specific features of iron overload in liver diseases other than haemochromatosis. PMID:17729389

Structure and function of enzymes in heme biosynthesis.

PubMed

Layer, Gunhild; Reichelt, Joachim; Jahn, Dieter; Heinz, Dirk W

2010-06-01

Tetrapyrroles like hemes, chlorophylls, and cobalamin are complex macrocycles which play essential roles in almost all living organisms. Heme serves as prosthetic group of many proteins involved in fundamental biological processes like respiration, photosynthesis, and the metabolism and transport of oxygen. Further, enzymes such as catalases, peroxidases, or cytochromes P450 rely on heme as essential cofactors. Heme is synthesized in most organisms via a highly conserved biosynthetic route. In humans, defects in heme biosynthesis lead to severe metabolic disorders called porphyrias. The elucidation of the 3D structures for all heme biosynthetic enzymes over the last decade provided new insights into their function and elucidated the structural basis of many known diseases. In terms of structure and function several rather unique proteins were revealed such as the V-shaped glutamyl-tRNA reductase, the dipyrromethane cofactor containing porphobilinogen deaminase, or the "Radical SAM enzyme" coproporphyrinogen III dehydrogenase. This review summarizes the current understanding of the structure-function relationship for all heme biosynthetic enzymes and their potential interactions in the cell.

The neuropsychiatric ailment of Vincent Van Gogh

PubMed Central

Bhattacharyya, Kalyan B.; Rai, Saurabh

2015-01-01

Vincent Van Gogh is one of the most celebrated creative artists of all time. All his life, he was afflicted by some kind of neurological or psychiatric disorder, which remains a mystery even today. Many historians and his personal physicians believe that he suffered from epilepsy while others felt that he was affected by Ménière's disease. Features such as hypergraphia, atypical sexuality, and viscosity of thinking suggest the possibility of Gastaut-Geschwind phenomenon, a known complication of complex partial seizure. On the contrary, some historians feel that he was forced to sever his right ear in order to get relief from troublesome tinnitus, a complication of Ménière's disease. He was addicted to the liquor absinthe, which is known to lead to xanthopsia, and many authorities argue that this was the reason for his penchant for the deep and bright yellow color in many of his paintings. Others have suggested the possibility of bipolar disorder, sunstroke, acute intermittent porphyria, and digitalis toxicity as well. PMID:25745302

From Flavr Savr Tomatoes to Stem Cell Therapy: Young People's Understandings of Gene Technology, 15 Years on

NASA Astrophysics Data System (ADS)

Lewis, Jenny

2014-02-01

This paper explores knowledge and understanding of basic genetics and gene technologies in school students who have been taught to a `science for all' National Curriculum and compares 482 students in 1995 (gene technology was a new and rapidly developing area of science with potential to impact on everyday life; the first cohort of students had been taught to the National Curriculum for Science) with 154 students in 2011 (genomics had replaced gene technology as a rapidly developing area of science with potential to impact on everyday life; science as a core subject within the National Curriculum was well established). These studies used the same questions, with the same age group (14-16) across the same (full) ability range; in addition the 2011 sample were asked about stem cells, stem cell technology and epigenetics. Students in 2011 showed: better knowledge of basic genetics but continuing difficulty in developing coherent explanatory frameworks; a good understanding of the nature of stem cells but no understanding of the process by which such cells become specialised; better understanding of different genetic technologies but also a wider range of misunderstandings and confusions (both between different genetic technologies and with other biological processes); continuing difficulty in evaluating potential veracity of short `news' items but greater awareness of ethical issues and the range of factors (including knowledge of genetics) which could be drawn on when justifying a view or coming to a decision. Implications for a `science for all' curriculum are considered.

Hearing Loss in Children

MedlinePlus

... Hearing Loss Homepage Basics Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2016 2015 2014 2013 ...

Oral Medication

MedlinePlus

... Honor Donation Donate by phone at 1-800-DIABETES (1-800-342-2383) Donate by mail Why Give? ... My Health Advisor Tools to Know Your Risk Diabetes Basics Symptoms Type 1 Type 2 Gestational Myths Statistics Common Terms Genetics ...

Weight Loss

MedlinePlus

... Honor Donation Donate by phone at 1-800-DIABETES (1-800-342-2383) Donate by mail Why Give? ... My Health Advisor Tools to Know Your Risk Diabetes Basics Symptoms Type 1 Type 2 Gestational Myths Statistics Common Terms Genetics ...

Understanding Carbohydrates

MedlinePlus

... Honor Donation Donate by phone at 1-800-DIABETES (1-800-342-2383) Donate by mail Why Give? ... My Health Advisor Tools to Know Your Risk Diabetes Basics Symptoms Type 1 Type 2 Gestational Myths Statistics Common Terms Genetics ...

A survey of application: genomics and genetic programming, a new frontier.

PubMed

Khan, Mohammad Wahab; Alam, Mansaf

2012-08-01

The aim of this paper is to provide an introduction to the rapidly developing field of genetic programming (GP). Particular emphasis is placed on the application of GP to genomics. First, the basic methodology of GP is introduced. This is followed by a review of applications in the areas of gene network inference, gene expression data analysis, SNP analysis, epistasis analysis and gene annotation. Finally this paper concluded by suggesting potential avenues of possible future research on genetic programming, opportunities to extend the technique, and areas for possible practical applications. Copyright © 2012 Elsevier Inc. All rights reserved.

Basic haemoglobinopathy diagnostics in Dutch laboratories; providing an informative test result.

PubMed

Kaufmann, J O; Smit, J W; Huisman, W; Idema, R N; Bakker, E; Giordano, P C

2013-08-01

After a first survey in 2001, the Dutch Association of Hematological Laboratory Research (VHL) advised its members to adopt a basic protocol for haemoglobinopathy carrier detection and to provide genetic information with all positive results to allow health-care professionals to inform carriers about potential genetic risks. This article reports on the compliance with these recommendations and their consequences. Clinical chemists of all 106 Dutch laboratories were invited to answer a survey on patient population, diagnostic techniques used, (self-reported) knowledge, use and effect of the additional information. The average increase in diagnostic output was over 60% and the recommended basic protocol was applied by 65% of the laboratories. Over 84% of the laboratories reported to be aware of the additional recommendations and 77% to be using them. Most laboratories with limited diagnostic requests were still sending their cases to other laboratories and included the genetic information received from these laboratories in their diagnostic reports. The effect of information on subsequent 'family analysis' was estimated to be between 26 and 50%. The present study shows an increase in diagnostic potential for haemoglobinopathy over the last decade, especially in the larger cities. Low 'family testing' rates were mostly found in areas with lower carrier prevalence or associated with local reluctance to pass the information to carriers. In spite of a dramatic improvement, too many carriers are still not informed because of lack of awareness among health-care providers and more education is needed. © 2012 John Wiley & Sons Ltd.

Translational genetics: advancing fronts for craniofacial health.

PubMed

D'Souza, R N; Dunnwald, M; Dunnvald, M; Frazier-Bowers, S; Polverini, P J; Wright, J T; de Rouen, T; Vieira, A R

2013-12-01

Scientific opportunities have never been better than today! The completion of the Human Genome project has sparked hope and optimism that cures for debilitating conditions can be achieved and tailored to individuals and communities. The availability of reference genome sequences and genetic variations as well as more precise correlations between genotype and phenotype have facilitated the progress made in finding solutions to clinical problems. While certain craniofacial and oral diseases previously deemed too difficult to tackle have benefited from basic science and technological advances over the past decade, there remains a critical need to translate the fruits of several decades' worth of basic and clinical research into tangible therapies that can benefit patients. The fifth Annual Fall Focused Symposium, "Translational Genetics - Advancing Fronts for Craniofacial Health", was created by the American Association for Dental Research (AADR) to foster its mission to advance interdisciplinary research that is directed toward improving oral health. The symposium showcased progress made in identifying molecular targets that are potential therapeutics for common and rare dental diseases and craniofacial disorders. Speakers focused on translational and clinical applications of their research and, where applicable, on strategies for new technologies and therapeutics. The critical needs to transfer new knowledge to the classroom and for further investment in the field were also emphasized. The symposium underscored the importance of basic research, chairside clinical observations, and population-based studies in driving the new translational connections needed for the development of cures for the most common and devastating diseases involving the craniofacial complex.

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

PubMed

Wilkes, Michael S; Day, Frank C; Fancher, Tonya L; McDermott, Haley; Lehman, Erik; Bell, Robert A; Green, Michael J

2017-09-13

Screening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions. One hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information. PCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients. While our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics.

Genetic dissection of main and epistatic effects of QTL based on augmented triple test cross design

PubMed Central

Zhang, Zheng; Dai, Zhijun; Chen, Yuan; Yuan, Xiong; Yuan, Zheming; Tang, Wenbang; Li, Lanzhi; Hu, Zhongli

2017-01-01

The use of heterosis has considerably increased the productivity of many crops; however, the biological mechanism underpinning the technique remains elusive. The North Carolina design III (NCIII) and the triple test cross (TTC) are powerful and popular genetic mating design that can be used to decipher the genetic basis of heterosis. However, when using the NCIII design with the present quantitative trait locus (QTL) mapping method, if epistasis exists, the estimated additive or dominant effects are confounded with epistatic effects. Here, we propose a two-step approach to dissect all genetic effects of QTL and digenic interactions on a whole genome without sacrificing statistical power based on an augmented TTC (aTTC) design. Because the aTTC design has more transformation combinations than do the NCIII and TTC designs, it greatly enriches the QTL mapping for studying heterosis. When the basic population comprises recombinant inbred lines (RIL), we can use the same materials in the NCIII design for aTTC-design QTL mapping with transformation combination Z1, Z2, and Z4 to obtain genetic effect of QTL and digenic interactions. Compared with RIL-based TTC design, RIL-based aTTC design saves time, money, and labor for basic population crossed with F1. Several Monte Carlo simulation studies were carried out to confirm the proposed approach; the present genetic parameters could be identified with high statistical power, precision, and calculation speed, even at small sample size or low heritability. Additionally, two elite rice hybrid datasets for nine agronomic traits were estimated for real data analysis. We dissected the genetic effects and calculated the dominance degree of each QTL and digenic interaction. Real mapping results suggested that the dominance degree in Z2 that mainly characterize heterosis showed overdominance and dominance for QTL and digenic interactions. Dominance and overdominance were the major genetic foundations of heterosis in rice. PMID:29240818

Multiple Myeloma Genomics: A Systematic Review.

PubMed

Weaver, Casey J; Tariman, Joseph D

2017-08-01

This integrative review describes the genomic variants that have been found to be associated with poor prognosis in patients diagnosed with multiple myeloma (MM). Second, it identifies MM genetic and genomic changes using next-generation sequencing, specifically whole-genome sequencing or exome sequencing. A search for peer-reviewed articles through PubMed, EBSCOhost, and DePaul WorldCat Libraries Worldwide yielded 33 articles that were included in the final analysis. The most commonly reported genetic changes were KRAS, NRAS, TP53, FAM46C, BRAF, DIS3, ATM, and CCND1. These genetic changes play a role in the pathogenesis of MM, prognostication, and therapeutic targets for novel therapies. MM genetics and genomics are expanding rapidly; oncology nurse clinicians must have basic competencies in genetics and genomics to help patients understand the complexities of genetic and genomic alterations and be able to refer patients to appropriate genomic professionals if needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Your Genes, Your Choices: Exploring the Issues Raised by Genetic Research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, C.

1999-05-31

Your Genes, Your Choices provides accurate information about the ethical, legal, and social implications of the Human Genome Project and genetic research in an easy-to-read style and format. Each chapter in the book begins with a brief vignette, which introduces an issue within a human story, and raises a question for the reader to think about as the basic science and information are presented in the rest of the chapter.

Developmental and Genetic Aspects of Clefting Disorders: A Clinical Approach

PubMed Central

Hanson, James W.; Thomson, Elizabeth J.; Muilrnnuth, Snn V.; Sandra, Alexander; Coan, Joan M.; Lipcamon, Larry D.; Hill, Ed

1990-01-01

This demonstration shows an interactive videodisc program that teaches the basic embryology of craniofacial development, the developmental and genetic aspects of orofacial clefts, and the process of diagnosing a patient with a clefting disorder. This program is designed for medical students, residents, and fellows in Pediatrics and Otolaryngology. It will also be of interest to members of cleft lip/palate teams. Imagesp1020-ap1021-ap1021-bp1021-c

Simulated breeding with QU-GENE graphical user interface.

PubMed

Hathorn, Adrian; Chapman, Scott; Dieters, Mark

2014-01-01

Comparing the efficiencies of breeding methods with field experiments is a costly, long-term process. QU-GENE is a highly flexible genetic and breeding simulation platform capable of simulating the performance of a range of different breeding strategies and for a continuum of genetic models ranging from simple to complex. In this chapter we describe some of the basic mechanics behind the QU-GENE user interface and give a simplified example of how it works.

ASHG activities relative to education: Human genetics as a component of medical school curricula: A report to the American society of human genetics

PubMed Central

Riccardi, Vincent M.; Schmickel, Roy D.

1988-01-01

In recent years, there has been a remarkable increase in both the rate of acquiring new information about human genetics and the importance of human genetics for modern health care. As a result, human genetics educators have queried whether the teaching of human genetics in North-American medical schools has kept pace with these increases. To address this question, a survey of these medical schools was undertaken to assess how human geneticists perceive the teaching of human genetics in their respective institutions. The results of the survey, begun and completed in 1985, indicate the following: (1) the teaching of human genetics in medical schools is extremely variable from one institution to another, with some schools having no identifiable human genetics teaching at all; (2) the relevance of human genetics to other basic science and clinical disciplines apparently leads to noncategorical or fragmented teaching of human genetics, which may also contribute to the absence of a specific medical school course in the subject; and (3) there is a need for closer collaboration between human genetics educators and their respective medical school administrators and curriculum committees. PMID:17948585

Editorial Commentary: A Model for Shoulder Rotator Cuff Repair and for Basic Science Investigations.

PubMed

Brand, Jefferson C

2018-04-01

"Breaking the fourth wall" is a theater convention where the narrator or character speaks directly to the audience. As an Assistant Editor-in-Chief, as I comment on a recent basic science study investigating rotator cuff repair, I break the fourth wall and articulate areas of basic science research excellence that align with the vision that we hold for our journal. Inclusion of a powerful video strengthens the submission. We prefer to publish clinical videos in our companion journal, Arthroscopy Techniques, and encourage basic science video submissions to Arthroscopy. Basic science research requires step-by-tedious-step analogous to climbing a mountain. Establishment of a murine rotator cuff repair model was rigorous and research intensive, biomechanically, radiographically, histologically, and genetically documented, a huge step toward the bone-to-tendon healing research summit. This research results in a model for both rotator cuff repair and the pinnacle of quality, basic science research. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Basics on Genes and Genetic Disorders

MedlinePlus

... kon-druh-PLAY-zhuh, a form of dwarfism), Marfan syndrome (a connective tissue disorder), and Huntington disease (a ... this topic for: Teens Albinism Muscular Dystrophy Dwarfism Marfan Syndrome Cystic Fibrosis Hemophilia von Willebrand Disease Having a ...

Beta

USDA-ARS?s Scientific Manuscript database

This chapter covers the use of wild beets in sugar beet improvement, including the basic botany of the species, its distribution; geographical locations of genetic diversity; morphology; cytology and karyotype; genome size; taxonomic position; agricultural status (model plant/weeds/invasive species/...

5-years later - have faculty integrated medical genetics into nurse practitioner curriculum?

PubMed

Maradiegue, Ann H; Edwards, Quannetta T; Seibert, Diane

2013-10-31

Abstract Many genetic/genomic educational opportunities are available to assist nursing faculty in their knowledge and understanding of genetic/genomics. This study was conducted to assess advance practice nursing faculty members' current knowledge of medical genetics/genomics, their integration of genetics/genomics content into advance practice nursing curricula, any prior formal training/education in genetics/genomics, and their comfort level in teaching genetics/genomic content. A secondary aim was to conduct a comparative analysis of the 2010 data to a previous study conducted in 2005, to determine changes that have taken place during that time period. During a national nurse practitioner faculty conference, 85 nurse practitioner faculty voluntarily completed surveys. Approximately 70% of the 2010 faculty felt comfortable teaching basic genetic/genomic concepts compared to 50% in 2005. However, there continue to be education gaps in the genetic/genomic content taught to advance practice nursing students. If nurses are going to be a crucial member of the health-care team, they must achieve the requisite competencies to deliver the increasingly complex care patients require.

Parental consent for bone marrow transplantation in the case of genetic disorders.

PubMed

Prows, C A; McCain, G C

1997-01-01

To describe the responses of mothers and fathers who were offered bone marrow transplantation (BMT) for their children with genetic disorders. Qualitative. Private hospital rooms/offices. Six mothers and 4 fathers of children with genetic disorders. The basic social-psychological problem confronting the parents was the conflicting alternatives of life versus death for their children. It was certain that these children would die from their genetic disorders but without having to endure the pain and suffering of a BMT. The BMT would be difficult, possibly resulting in death, but with a chance of survival. Parents believed that BMT was the only chance of survival for their children, leaving them no choice except to pursue the BMT treatment.

Demographic Events and Evolutionary Forces Shaping European Genetic Diversity

PubMed Central

Veeramah, Krishna R.; Novembre, John

2014-01-01

Europeans have been the focus of some of the largest studies of genetic diversity in any species to date. Recent genome-wide data have reinforced the hypothesis that present-day European genetic diversity is strongly correlated with geography. The remaining challenge now is to understand more precisely how patterns of diversity in Europe reflect ancient demographic events such as postglacial expansions or the spread of farming. It is likely that recent advances in paleogenetics will give us some of these answers. There has also been progress in identifying specific segments of European genomes that reflect adaptations to selective pressures from the physical environment, disease, and dietary shifts. A growing understanding of how modern European genetic diversity has been shaped by demographic and evolutionary forces is not only of basic historical and anthropological interest but also aids genetic studies of disease. PMID:25059709

[The genetic control of mouse coat color and its applications in genetics teaching].

PubMed

Xing, Wanjin; Morigen, Morigen

2014-10-01

Mice are the most commonly used mammalian model. The coat colors of mice are typical Mendelian traits, which have various colors such as white, black, yellow and agouti. The inheritance of mouse coat color is usually stated as an example only in teaching the knowledge of recessive lethal alleles. After searched the related literatures and summarized the molecular mechanisms of mouse coat color inheritance, we further expanded the application of this example into the introduction of the basic concepts of alleles and Mendelian laws, demonstration of the gene structure and function, regulation of gene expression, gene interaction, epigenetic modification, quantitative genetics, as well as evolutionary genetics. By running this example through the whole genetics-teaching lectures, we help the student to form a systemic and developmental view of genetic analysis. At the same time, this teaching approach not only highlights the advancement and integrity of genetics, but also results in a good teaching effect on inspiring the students' interest and attracting students' attention.

Genetic testing in heritable cardiac arrhythmia syndromes: differentiating pathogenic mutations from background genetic noise.

PubMed

Giudicessi, John R; Ackerman, Michael J

2013-01-01

In this review, we summarize the basic principles governing rare variant interpretation in the heritable cardiac arrhythmia syndromes, focusing on recent advances that have led to disease-specific approaches to the interpretation of positive genetic testing results. Elucidation of the genetic substrates underlying heritable cardiac arrhythmia syndromes has unearthed new arrhythmogenic mechanisms and given rise to a number of clinically meaningful genotype-phenotype correlations. As such, genetic testing for these disorders now carries important diagnostic, prognostic, and therapeutic implications. Recent large-scale systematic studies designed to explore the background genetic 'noise' rate associated with these genetic tests have provided important insights and enhanced how positive genetic testing results are interpreted for these potentially lethal, yet highly treatable, cardiovascular disorders. Clinically available genetic tests for heritable cardiac arrhythmia syndromes allow the identification of potentially at-risk family members and contribute to the risk-stratification and selection of therapeutic interventions in affected individuals. The systematic evaluation of the 'signal-to-noise' ratio associated with these genetic tests has proven critical and essential to assessing the probability that a given variant represents a rare pathogenic mutation or an equally rare, yet innocuous, genetic bystander.

Xenobiology: State-of-the-Art, Ethics, and Philosophy of New-to-Nature Organisms.

PubMed

Schmidt, Markus; Pei, Lei; Budisa, Nediljko

The basic chemical constitution of all living organisms in the context of carbon-based chemistry consists of a limited number of small molecules and polymers. Until the twenty-first century, biology was mainly an analytical science and has now reached a point where it merges with engineering science, paving the way for synthetic biology. One of the objectives of synthetic biology is to try to change the chemical compositions of living cells, that is, to create an artificial biological diversity, which in turn fosters a new sub-field of synthetic biology, xenobiology. In particular, the genetic code in living systems is based on highly standardized chemistry composed of the same "letters" or nucleotides as informational polymers (DNA, RNA) and the 20 amino acids which serve as basic building blocks for proteins. The universality of the genetic code enables not only vertical gene transfer within the same species but also horizontal gene transfer across biological taxa, which require a high degree of standardization and interconnectivity. Although some minor alterations of the standard genetic code are found in nature (e.g., proteins containing non-conical amino acids exist in nature, and some organisms use alternated coding systems), all structurally deep chemistry changes within living systems are generally lethal, making the creation of artificial biological system an extremely difficult challenge.In this context, one of the great challenges for bioscience is the development of a strategy for expanding the standard basic chemical repertoire of living cells. Attempts to alter the meaning of the genetic information stored in DNA as an informational polymer by changing the chemistry of the polymer (i.e., xeno-nucleic acids) or by changes in the genetic code have already yielded successful results. In the future this should enable the partial or full redirection of the biological information flow to generate "new" version(s) of the genetic code derived from the "old" biological world.In addition to the scientific challenges, the attempt to increase biochemical diversity also raises important ethical and philosophical issues. Although promotors of this branch of synthetic biology highlight the many potential applications to come (e.g., novel tools for diagnostics and fighting infection diseases), such developments could also bring risks affecting social, political, and other structures of nearly all societies.

Investigating Genomic Mechanisms of Treatment Resistance in Castration Resistant Prostate Cancer

DTIC Science & Technology

2015-05-01

and genomically profiled. Figure 3 shows data from a series of cell- line experiments showing that PC3 prostate cancer cells are recoverable and...coursework until the second-half of the grant period. I am enrolled in the UCSF Biomedical Sciences Graduate Program class BMS 255: Genetics : Basic... Genetics and Genomics. This class is set to start in January 2016. Given a large number of clinical, teaching, and research duties I will plan to enroll

Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature.

PubMed

Narumi, Yoko; Nishina, Sachiko; Tokimitsu, Motoharu; Aoki, Yoko; Kosaki, Rika; Wakui, Keiko; Azuma, Noriyuki; Murata, Toshinori; Takada, Fumio; Fukushima, Yoshimitsu; Kosho, Tomoki

2014-05-01

Congenital cataracts are the most important cause of severe visual impairment in infants. Genetic factors contribute to the disease development and 29 genes are known to cause congenital cataracts. Identifying the genetic cause of congenital cataracts can be difficult because of genetic heterogeneity. V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) encodes a basic region/leucine zipper transcription factor that plays a key role as a regulator of embryonic lens fiber cell development. MAF mutations have been reported to cause juvenile-onset pulverulent cataract, microcornea, iris coloboma, and other anterior segment dysgenesis. We report on six patients in a family who have congenital cataracts were identified MAF mutation by whole exome sequencing (WES). The heterozygous MAF mutation Q303L detected in the present family occurs in a well conserved glutamine residue at the basic region of the DNA-binding domain. All affected members showed congenital cataracts. Three of the six members showed microcornea and one showed iris coloboma. Congenital cataracts with MAF mutation exhibited phenotypically variable cataracts within the family. Review of the patients with MAF mutations supports the notion that congenital cataracts caused by MAF mutations could be accompanied by microcornea and/or iris coloboma. WES is a useful tool for detecting disease-causing mutations in patients with genetically heterogeneous conditions. © 2014 Wiley Periodicals, Inc.

International Szent-Györgyi Prize for Progress in Cancer Research: basic and translational research recognition : Mary-Claire King received the 2016 Prize for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer.

PubMed

Hartmann, Hali; Zhao, Jie; Ba, Sujuan

2017-11-21

The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientific award sponsored by the National Foundation for Cancer Research (NFCR)-a leading cancer research charitable organization in the United States that supports innovative cancer research globally with the ultimate goal to cure cancer. The coveted Szent-Györgyi Prize annually honors a scientist whose seminal discovery or body of work has resulted in, or led toward, notable contributions to cancer prevention, diagnosis, or treatment; and the discovery has had a high direct impact of saving people's lives. In addition, the prize promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. In 2016, NFCR's Szent-Györgyi Prize Selection Committee was unanimous in its decision to recognize an icon in human disease genetics, Dr. Mary-Claire King, for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer. Her proof of existence of BRCA1 gene and its location has made genetic screening for breast and ovarian cancers possible, saving lives of many people who are at high risk with inherited BRCA1 mutations.

American Society of Neuroradiology

MedlinePlus

... Tumors of the Central Nervous System: A Practical Approach for Gliomas, Part 1. Basic Tumor Genetics The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Practical Approach for Gliomas, Part 2. Isocitrate Dehydrogenase Status—Imaging ...

Advancing pig cloning technologies towards application in regenerative medicine.

PubMed

Nagashima, H; Matsunari, H; Nakano, K; Watanabe, M; Umeyama, K; Nagaya, M

2012-08-01

Regenerative medicine is expected to make a significant contribution by development of novel therapeutic treatments for intractable diseases and for improving the quality of life of patients. Many advances in regenerative medicine, including basic and translational research, have been developed and tested in experimental animals; pigs have played an important role in various aspects of this work. The value of pigs as a model species is being enhanced by the generation of specially designed animals through cloning and genetic modifications, enabling more sophisticated research to be performed and thus accelerating the clinical application of regenerative medicine. This article reviews the significant aspects of the creation and application of cloned and genetically modified pigs in regenerative medicine research and considers the possible future directions of the technology. We also discuss the importance of reproductive biology as an interface between basic science and clinical medicine. © 2012 Blackwell Verlag GmbH.

Allelic variants of hereditary prions: The bimodularity principle.

PubMed

Tikhodeyev, Oleg N; Tarasov, Oleg V; Bondarev, Stanislav A

2017-01-02

Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either "canonical" (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as "gene" and "allele" to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor.

Interfacing microbiology and biotechnology. Conference abstracts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maupin, Julia A.

2001-05-19

The Interfacing Microbiology and Biotechnology Conference was attended by over 100 faculty, post-docs, students, and research scientists from the US, Europe, and Latin America. The conference successfully stimulated communication and the dissemination of knowledge among scientists involved in basic and applied research. The focus of the conference was on microbial physiology and genetics and included sessions on C1 metabolism, archaeal metabolism, proteases and chaperones, gene arrays, and metabolic engineering. The meeting provided the setting for in-depth discussions between scientists who are internationally recognized for their research in these fields. The following objectives were met: (1) The promotion of interaction andmore » future collaborative projects among scientists involved in basic and applied research which incorporates microbial physiology, genetics, and biochemistry; (2) the facilitation of communication of new research findings through seminars, posters, and abstracts; (3 ) the stimulation of enthusiasm and education among participants including graduate and undergraduate students.« less

Allelic variants of hereditary prions: The bimodularity principle

PubMed Central

Tikhodeyev, Oleg N.; Tarasov, Oleg V.; Bondarev, Stanislav A.

2017-01-01

ABSTRACT Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either “canonical” (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as “gene” and “allele” to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor. PMID:28281926

Methods for genetic transformation of filamentous fungi.

PubMed

Li, Dandan; Tang, Yu; Lin, Jun; Cai, Weiwen

2017-10-03

Filamentous fungi have been of great interest because of their excellent ability as cell factories to manufacture useful products for human beings. The development of genetic transformation techniques is a precondition that enables scientists to target and modify genes efficiently and may reveal the function of target genes. The method to deliver foreign nucleic acid into cells is the sticking point for fungal genome modification. Up to date, there are some general methods of genetic transformation for fungi, including protoplast-mediated transformation, Agrobacterium-mediated transformation, electroporation, biolistic method and shock-wave-mediated transformation. This article reviews basic protocols and principles of these transformation methods, as well as their advantages and disadvantages.

DNA recombination protein-dependent mechanism of homoplasmy and its proposed functions.

PubMed

Shibata, Takehiko; Ling, Feng

2007-01-01

Homoplasmy is a basic genetic state of mitochondria, in which all of the hundreds to thousands of mitochondrial (mt)DNA copies within a cell or an individual have the same nucleotide-sequence. It was recently found that "vegetative segregation" to generate homoplasmic cells is an active process under genetic control. In the yeast Saccharomyces cerevisiae, the Mhr1 protein which catalyzes a key reaction in mtDNA homologous recombination, plays a pivotal role in vegetative segregation. Conversely, within the nuclear genome, homologous DNA recombination causes genetic diversity. Considering these contradictory roles of this key reaction in DNA recombination, possible functions of homoplasmy are discussed.

Physical methods for genetic plant transformation

NASA Astrophysics Data System (ADS)

Rivera, Ana Leonor; Gómez-Lim, Miguel; Fernández, Francisco; Loske, Achim M.

2012-09-01

Production of transgenic plants is a routine process for many crop species. Transgenes are introduced into plants to confer novel traits such as improved nutritional qualities, tolerance to pollutants, resistance to pathogens and for studies of plant metabolism. Nowadays, it is possible to insert genes from plants evolutionary distant from the host plant, as well as from fungi, viruses, bacteria and even animals. Genetic transformation requires penetration of the transgene through the plant cell wall, facilitated by biological or physical methods. The objective of this article is to review the state of the art of the physical methods used for genetic plant transformation and to describe the basic physics behind them.

Important role of translational science in rare disease innovation, discovery, and drug development.

PubMed

Pariser, Anne R; Gahl, William A

2014-08-01

Rare diseases play a leading role in innovation and the advancement of medical and pharmaceutical science. Most rare diseases are genetic disorders or atypical manifestations of infectious, immunologic, or oncologic diseases; they all provide opportunities to study extremes of human pathology and provide insight into both normal and aberrant physiology. Recently, drug development has become increasingly focused on classifying diseases largely on genetic grounds; this has allowed the identification of molecularly defined targets and the development of targeted therapies. Clinical trials are now focusing on progressively smaller subgroups within both common and rare disease populations, often based on genetic tests or biomarkers. Drug developers, researchers, and regulatory agencies face a variety of challenges throughout the life cycle of drug research and development for rare diseases. These include the small numbers of patients available for study, lack of knowledge of the disease's natural history, incomplete understanding of the basic mechanisms causing the disorder, and variability in disease severity, expression, and course. Traditional approaches to rare disease clinical research have not kept pace with advances in basic science, and increased attention to translational science is needed to address these challenges, especially diagnostic testing, registries, and novel trial designs.

Light Vision Color

NASA Astrophysics Data System (ADS)

Valberg, Arne

2005-04-01

Light Vision Color takes a well-balanced, interdisciplinary approach to our most important sensory system. The book successfully combines basics in vision sciences with recent developments from different areas such as neuroscience, biophysics, sensory psychology and philosophy. Originally published in 1998 this edition has been extensively revised and updated to include new chapters on clinical problems and eye diseases, low vision rehabilitation and the basic molecular biology and genetics of colour vision. Takes a broad interdisciplinary approach combining basics in vision sciences with the most recent developments in the area Includes an extensive list of technical terms and explanations to encourage student understanding Successfully brings together the most important areas of the subject in to one volume

Asilomar Decision: Unprecedented Guidelines for Gene-Transplant Research

ERIC Educational Resources Information Center

Science News, 1975

1975-01-01

The hazards posed by new techniques of genetic manipulation have prompted scientists to regulate and in some cases restrict their own basic investigations. Describes some possible applications of the new techniques and outlines the established research guidelines. (GS)

Genetics Home Reference: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

MedlinePlus

... my area? Other Names for This Condition MELAS MELAS syndrome mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like ... basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci. 2008 Oct;1142: ...

Risk of Bacterial Meningitis in Children with Cochlear Implants

MedlinePlus

... Hearing Loss Homepage Basics Noise-Induced Hearing Loss Genetics of Hearing Loss Screening & Diagnosis Types of Hearing Loss About Sound Treatment & Intervention Services Learning Language Bacterial Meningitis Studies Data & Statistics EHDI Annual Data 2016 2015 2014 2013 ...

Genetic and teratological considerations in the analysis of concordant and discordant abnormalities in twins.

PubMed

Gericke, G S

1986-01-18

Results from monozygotic (MZ) and dizygotic (DZ) twin research are often used in an attempt to gain a clearer understanding of the 'nature v. nurture' dilemma. Discordance between MZ twins has been considered to be environmental, and greater concordance in MZ compared with DZ pairs to be genetic. Current genetic and teratological theories considerably complicate the interpretation of concordance and discordance of abnormalities. The high rate of discordant intra-uterine death recently demonstrated in twins may profoundly influence the value of epidemiological studies usually performed in later life. Furthermore, indirect zygosity estimations based on sex ratios in DZ twins may be flawed because it is now recognized that increasing numbers of conditions are genetically heterogeneous. Emphasis is laid on problems of interpretation of discordance and concordance for developmental abnormalities in twins, and some possible mechanisms for their induction are discussed. Basic genetic concepts relevant to the expression of abnormalities in twins are outlined.

The Clinical Delivery of Pharmacogenetic Testing Services: A Proposed Partnership between Genetic Counselors and Pharmacists

PubMed Central

Mills, Rachel; Haga, Susanne B.

2013-01-01

One of the basic questions in the early uses of pharmacogenetic (PGx) testing revolves around the clinical delivery of testing. Because multiple health professionals may play a role in the delivery of PGx testing, various clinical delivery models have begun to be studied. We propose that a partnership between genetic counselors and pharmacists can assist clinicians in the delivery of comprehensive PGx services. Based on their expert knowledge of pharmacokinetics and pharmacodynamics, pharmacists can facilitate the appropriate application of PGx test results to adjust medication use as warranted and act as a liaison to the healthcare team recommending changes in medication based on test results and patient input. Genetic counselors are well-trained in genetics as well as risk communication and counseling methodology, but have limited knowledge of pharmaceuticals. The complementary knowledge and skill set supports the partnership between genetic counselors and pharmacists to provide effective PGx testing services. PMID:23746189

A serious gaming/immersion environment to teach clinical cancer genetics.

PubMed

Nosek, Thomas M; Cohen, Mark; Matthews, Anne; Papp, Klara; Wolf, Nancy; Wrenn, Gregg; Sher, Andrew; Coulter, Kenneth; Martin, Jessica; Wiesner, Georgia L

2007-01-01

We are creating an interactive, simulated "Cancer Genetics Tower" for the self-paced learning of Clinical Cancer Genetics by medical students (go to: http://casemed.case.edu/cancergenetics). The environment uses gaming theory to engage the students into achieving specific learning objectives. The first few levels contain virtual laboratories where students achieve the basic underpinnings of Cancer Genetics. The next levels apply these principles to clinical practice. A virtual attending physician and four virtual patients, available for questioning through virtual video conferencing, enrich each floor. The pinnacle clinical simulation challenges the learner to integrate all information and demonstrate mastery, thus "winning" the game. A pilot test of the program by 17 medical students yielded very favorable feedback; the students found the Tower a "great way to teach", it held their attention, and it made learning fun. A majority of the students preferred the Tower over other resources to learn Cancer Genetics.

An efficient and rapid influenza gene cloning strategy for reverse genetics system.

PubMed

Shao, Hongxia; Fan, Zhonglei; Wan, Zhimin; Tian, Xiaoyan; Chen, Hongjun; Perez, Daniel R; Qin, Aijian; Ye, Jianqiang

2015-09-15

Influenza reverse genetics plays vital roles in understanding influenza molecular characteristics and vaccine development. However, current influenza reverse genetics heavily depends on restriction enzyme and ligation for gene cloning. The traditional cloning process of influenza eight fragments for virus rescuing generally requires considerable work. To simplify and increase the pace of gene cloning for influenza reverse genetics system, we developed a rapid restriction enzyme-free ExnaseTM II-based in vitro recombination approach for influenza gene cloning. We used this strategy rapidly and successfully to clone influenza eight genes both from viruses PR8 and H9N2 for virus rescuing. Our data demonstrate that the strategy developed here can accelerate the process of influenza gene cloning into reverse genetics system, and shows high potential for applications in both influenza basic and applied research. Copyright © 2015 Elsevier B.V. All rights reserved.

Genomics of mucoepidermoid and adenoid cystic carcinomas.

PubMed

Yan, Kenneth; Yesensky, Jessica; Hasina, Rifat; Agrawal, Nishant

2018-02-01

To report on the current state of the literature on the genetics of mucoepidermoid and adenoid cystic carcinomas of the salivary glands with a focus on genomic screens and recently discovered genetic translocations. A PubMed based literature review was performed to query for genetics related basic science and preclinical studies about mucoepidermoid and adenoid cystic carcinomas of the salivary glands. Genetic translocations between CRTC1 and MAML2 in mucoepidermoid carcinoma and between MYB and NFIB in adenoid cystic carcinoma have been recently discovered and have therapeutic implications. Key signaling pathways such as the EGFR pathway in mucoepidermoid carcinoma and the Notch pathway, chromatin regulation, and c-kit mediated epithelial-mesenchymal transitions in adenoid cystic carcinoma have recently been elucidated, pointing to possible therapeutic targets in both cancers.

Genomics of mucoepidermoid and adenoid cystic carcinomas

PubMed Central

Yan, Kenneth; Yesensky, Jessica; Hasina, Rifat

2018-01-01

Objective To report on the current state of the literature on the genetics of mucoepidermoid and adenoid cystic carcinomas of the salivary glands with a focus on genomic screens and recently discovered genetic translocations. Methods A PubMed based literature review was performed to query for genetics related basic science and preclinical studies about mucoepidermoid and adenoid cystic carcinomas of the salivary glands. Results and conclusions Genetic translocations between CRTC1 and MAML2 in mucoepidermoid carcinoma and between MYB and NFIB in adenoid cystic carcinoma have been recently discovered and have therapeutic implications. Key signaling pathways such as the EGFR pathway in mucoepidermoid carcinoma and the Notch pathway, chromatin regulation, and c‐kit mediated epithelial‐mesenchymal transitions in adenoid cystic carcinoma have recently been elucidated, pointing to possible therapeutic targets in both cancers. PMID:29492469

Materials of the final reports on the joint Soviet-American experiment on the Kosmos-936 biosatellite

NASA Technical Reports Server (NTRS)

Timofeyev-Resolskiy, N. V.; Parfenov, G. P.; Tairbekov, M.; Platonova, R. N.; Rostopshina, A. V.; Zhvalikovskaya, V. P.; Mosgovaya, I. Y.; Shvets, V. N.; Kovalev, Y. Y.; Dudkin, V. Y.

1978-01-01

Biological experiments onboard the Kosmos-936 investigated the effect of weightlessness on the basic components of cells, the genetic structure and energy apparatus. Genetic studies were made on the Drosophila melanogaster. Experiments were made on higher vegetation and fungi as well. The results indicate that weightlessness cannot be the principal barrier for normal development. An experiment with ectopic osteogenesis in weightlessness was carried out. Measurements were made of cosmic radiation inside and outside the biosatellite.

Genetic Breeding and Diversity of the Genus Passiflora: Progress and Perspectives in Molecular and Genetic Studies

PubMed Central

Cerqueira-Silva, Carlos Bernard M.; Jesus, Onildo N.; Santos, Elisa S. L.; Corrêa, Ronan X.; Souza, Anete P.

2014-01-01

Despite the ecological and economic importance of passion fruit (Passiflora spp.), molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i) to present the current condition of the passion fruit crop; (ii) to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii) to present the contributions of genetic engineering for passion fruit culture; and (iv) to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit. PMID:25196515

What are the priorities in basic asthma research? A United Kingdom perspective.

PubMed

Hallsworth, Matthew P; Major, Philippa J; Barnes, Jack; Lee, Tak H

2003-02-01

The National Asthma Campaign (in the United Kingdom) has recently completed a strategic review of priorities for basic asthma research over the next 5 to 10 years. Leading asthma experts and representatives of the main funding agencies were involved in a nationwide consultation. Discussions were carried out in 7 thematic areas: Genetics of asthma, early-life events, environmental influences, immunology and immunotherapy, inflammation and anti-inflammation, airway remodeling, and the interface between academia and industry. Discussions were not restricted by considerations of financial affordability but were driven by vision and science. The consultation highlighted a number of generic issues pertaining to the organization of basic asthma research. Phenotypes of asthma require more robust characterization, particularly for genetic studies. Emphasis on longitudinal studies should be encouraged, and more information can still be gained from existing well-characterized asthma cohorts, though this requires some coordination. Human research is particularly strong and should continue, and the use of human tissue is vital to our understanding of the disease at the cellular and molecular levels. Animal models of asthma remain an important tool with which to dissect disease mechanisms, but they must be improved and refined. The consultation covered a wide range of issues and highlighted the need for collaboration at all levels between research groups and with industry and also between funding agencies. The recommendations made have relevance to everyone involved in basic asthma research. This article describes the recommendations and reviews the specific research issues relating to each of the 7 thematic areas.

Research advances on microbial genetics in China in 2015.

PubMed

Xie, Jian-ping; Han, Yu-bo; Liu, Gang; Bai, Lin-quan

2016-09-01

In 2015, there are significant progresses in many aspects of the microbial genetics in China. To showcase the contribution of Chinese scientists in microbial genetics, this review surveys several notable progresses in microbial genetics made largely by Chinese scientists, and some key findings are highlighted. For the basic microbial genetics, the components, structures and functions of many macromolecule complexes involved in gene expression regulation have been elucidated. Moreover, the molecular basis underlying the recognition of foreign nucleic acids by microbial immune systems was unveiled. We also illustrated the biosynthetic pathways and regulators of multiple microbial compounds, novel enzyme reactions, and new mechanisms regulating microbial gene expression. And new findings were obtained in the microbial development, evolution and population genetics. For the industrial microbiology, more understanding on the molecular basis of the microbial factory has been gained. For the pathogenic microbiology, the genetic circuits of several pathogens were depicted, and significant progresses were achieved for understanding the pathogen-host interaction and revealing the genetic mechanisms underlying antimicrobial resistance, emerging pathogens and environmental microorganisms at the genomic level. In future, the genetic diversity of microbes can be used to obtain specific products, while gut microbiome is gathering momentum.

Something's Fishy in Paxton Lake: A Case on Speciation in Sticklebacks.

ERIC Educational Resources Information Center

Sharp, Joan

2002-01-01

Introduces a case study on speciation and evolutionary mechanisms. Teaches science process skills as well as natural selection, biological species concepts, basic genetic terminology, and classification. Includes teaching notes and classroom management strategies. (Contains 14 references.) (YDS)

Methods in molecular biology: plant cytogenetics

USDA-ARS?s Scientific Manuscript database

Cytogenetic studies have contributed greatly to our understanding of genetics, biology, reproduction, and evolution. From early studies in basic chromosome behavior the field has expanded enabling whole genome analysis to the manipulation of chromosomes and their organization. This book covers a ran...

Commentary: Prerequisite Knowledge

ERIC Educational Resources Information Center

Taylor, Ann T. S.

2013-01-01

Most biochemistry, genetics, cell biology, and molecular biology classes have extensive prerequisite or co-requisite requirements, often including introductory chemistry, introductory biology, and organic chemistry coursework. But what is the function of these prerequisites? While it seems logical that a basic understanding of biological and…

Centromere synteny among Brachypodium, wheat, and rice

USDA-ARS?s Scientific Manuscript database

Rice, wheat and Brachypodium are plant genetic models with variable genome complexity and basic chromosome numbers, representing two subfamilies of the Poaceae. Centromeres are prominent chromosome landmarks, but their fate during this convoluted chromosome evolution has been more difficult to deter...

Hemiclonal analysis reveals significant genetic, environmental and genotype x environment effects on sperm size in Drosophila melanogaster.

PubMed

Morrow, E H; Leijon, A; Meerupati, A

2008-11-01

Spermatozoa are the most diverse of all animal cells. Variation in size alone is enormous and yet there are still no clear evolutionary explanations that can account for such diversity. The basic genetics of sperm form is also poorly understood, although sperm size is known to have a strong genetic component. Here, using hemiclonal analysis of Drosophila melanogaster, we demonstrate that there is not only a significant additive genetic component contributing to phenotypic variation in sperm length but also a significant environmental effect. Furthermore, the plasticity of sperm size has a significant genetic component to it (a genotype x environment interaction). A genotype x environment interaction could contribute to the maintenance of the substantial genetic variation in this trait and thereby explain the persistent inter-male differences in sperm size seen in numerous taxa. We suggest that the low conditional dependence and high heritability but low evolvability (the coefficient of additive genetic variation) of sperm length is more consistent with a history of stabilizing selection rather than either sexual selection or strong directional selection.

From Genetics to Genomics: A Short Introduction for Pediatric Neurologists.

PubMed

Neubauer, Bernd A; Lemke, Johannes R

2016-01-01

It is estimated that in humans approximately 50% of all 22500 genes are needed for the development and maintenance of the nervous system. The introduction of high-throughput technology in genetic analysis has therefore major implications, not only for the investigation of specific disease entities but also for the diagnostic workup of single individuals with neurologic disorders of genetic origin. A short primer for clinicians is presented, addressing aspects of current developments in medical genomics. Significant findings of the last years are exemplified in an educational manner to provide a basic understanding of disease mechanisms that were unraveled by recent genomic analysis. Georg Thieme Verlag KG Stuttgart · New York.

Genetic diversity of neotropical primates: phylogeny, population genetics, and animal models for infectious diseases.

PubMed

Moreira, M A M; Bonvicino, C R; Soares, M A; Seuánez, H N

2010-01-01

The classification of neotropical primates has been controversial, and different arrangements have been proposed based on disparate taxonomic criteria and on the traits selected for elucidating phylogenetic reconstructions, like morphologic characters, nuclear DNA and mitochondrial DNA. Population studies of some neotropical primates have been useful for assessing their extant genetic variability and for understanding their social structure and dynamics. Finally, neotropical primates have become valuable models for some human infectious deseases, especially for HIV studies related to viral resistance. In this review, we comment on these aspects that make neotropical primates a group of highly valuable species for basic and applied research. Copyright 2010 S. Karger AG, Basel.

Using the Molecular Classification of Glioblastoma to Inform Personalized Treatment

PubMed Central

Olar, Adriana; Aldape, Kenneth D.

2014-01-01

Glioblastoma is the most common and most aggressive diffuse glioma, associated with short survival and uniformly fatal outcome irrespective of treatment. It is characterized by morphologic, genetic, and gene-expression heterogeneity. The current standard of treatment is maximal surgical resection, followed by radiation, with concurrent and adjuvant chemotherapy. Due to the heterogeneity most tumors develop resistance to treatment and shortly recur. Following recurrence glioblastoma is quickly fatal in the majority of cases. Recent genetic molecular advances have contributed to a better understanding of glioblastoma pathophysiology and disease stratification. In this paper we review the basic glioblastoma pathophysiology with emphasis on clinically relevant genetic molecular alterations and potential targets for further drug development. PMID:24114756

Commercialization, patents and moral assessment of biotechnology products.

PubMed

Hoedemaekers, R

2001-06-01

The biotechnology patent debates have revealed deep moral concerns about basic genetics research, R&D and specific biotechnological products, concerns that are seldom taken into consideration in Technology Assessment. In this paper important moral concerns are examined which appear at the various stages of development of a specific genetic product: a predictive genetic test. The purpose is to illustrate the need for a more contextual approach in technology assessment, which integrates the various forms of interaction between bio-technology and society or societal segments. Such an approach will generate greater insight in the moral issues at all stages of a product's life-cycle and this will facilitate decision-making on the 'morality' of a specific biotechnological product.

Multi-objective optimization in systematic conservation planning and the representation of genetic variability among populations.

PubMed

Schlottfeldt, S; Walter, M E M T; Carvalho, A C P L F; Soares, T N; Telles, M P C; Loyola, R D; Diniz-Filho, J A F

2015-06-18

Biodiversity crises have led scientists to develop strategies for achieving conservation goals. The underlying principle of these strategies lies in systematic conservation planning (SCP), in which there are at least 2 conflicting objectives, making it a good candidate for multi-objective optimization. Although SCP is typically applied at the species level (or hierarchically higher), it can be used at lower hierarchical levels, such as using alleles as basic units for analysis, for conservation genetics. Here, we propose a method of SCP using a multi-objective approach. We used non-dominated sorting genetic algorithm II in order to identify the smallest set of local populations of Dipteryx alata (baru) (a Brazilian Cerrado species) for conservation, representing the known genetic diversity and using allele frequency information associated with heterozygosity and Hardy-Weinberg equilibrium. We worked in 3 variations for the problem. First, we reproduced a previous experiment, but using a multi-objective approach. We found that the smallest set of populations needed to represent all alleles under study was 7, corroborating the results of the previous study, but with more distinct solutions. In the 2nd and 3rd variations, we performed simultaneous optimization of 4 and 5 objectives, respectively. We found similar but refined results for 7 populations, and a larger portfolio considering intra-specific diversity and persistence with populations ranging from 8-22. This is the first study to apply multi-objective algorithms to an SCP problem using alleles at the population level as basic units for analysis.

A roadmap for bridging basic and applied research in forensic entomology.

PubMed

Tomberlin, J K; Mohr, R; Benbow, M E; Tarone, A M; VanLaerhoven, S

2011-01-01

The National Research Council issued a report in 2009 that heavily criticized the forensic sciences. The report made several recommendations that if addressed would allow the forensic sciences to develop a stronger scientific foundation. We suggest a roadmap for decomposition ecology and forensic entomology hinging on a framework built on basic research concepts in ecology, evolution, and genetics. Unifying both basic and applied research fields under a common umbrella of terminology and structure would facilitate communication in the field and the production of scientific results. It would also help to identify novel research areas leading to a better understanding of principal underpinnings governing ecosystem structure, function, and evolution while increasing the accuracy of and ability to interpret entomological evidence collected from crime scenes. By following the proposed roadmap, a bridge can be built between basic and applied decomposition ecology research, culminating in science that could withstand the rigors of emerging legal and cultural expectations.

Relationship of cooked rice nutritionally-important starch fractions with other physicochemical properties.

USDA-ARS?s Scientific Manuscript database

Sixteen rice cultivars representing 5 cytosine-thymine repeat (CTn) microsatellite genetic marker groups were analyzed for their cooked rice nutritionally-important starch fractions (rapidly digestible, slowly digestible, and resistant starch), basic grain quality indices (apparent amylose, crude pr...

Brain Structure and Development.

ERIC Educational Resources Information Center

Teyler, T.J.; Chiaia, N.

1983-01-01

Considers basic biology of brain, what is known of how it operates, and something of how it develops. Discusses properties of neurons and specialized regions of the brain in linguistic and higher order processing skills, as well as genetic and environmental influences on brain development. (CMG)

Adolescent Depression.

ERIC Educational Resources Information Center

Evans, Dina M.

Affective disorder is characterized by maladaptive changes in mood, attitudes, energy level, and physical status. These changes constitute the basic dimensions of depression. Depression results from a combination of genetic and experiential factors. There are sex differences and age differences with regard to depression, and there is a high…

Eukaryotic acquisition of a bacterial operon

USDA-ARS?s Scientific Manuscript database

The yeast Saccharomyces cerevisiae is one of the champions of basic biomedical research due to its compact eukaryotic genome and ease of experimental manipulation. Despite these immense strengths, its impact on understanding the genetic basis of natural phenotypic variation has been limited by strai...

Using a Genetic Algorithm to Design Nuclear Electric Spacecraft

NASA Technical Reports Server (NTRS)

Pannell, William P.

2003-01-01

The basic approach to to design nuclear electric spacecraft is to generate a group of candidate designs, see how "fit" the design are, and carry best design forward to the next generation. Some designs eliminated, some randomly modified and carried forward.

The nature of individual differences in inhibited temperament and risk for psychiatric disease: a review and meta-analysis

PubMed Central

Clauss, J. A.; Avery, S. N.; Blackford, J. U.

2015-01-01

What makes us different from one another? Why does one person jump out of airplanes for fun while another prefers to stay home and read? Why are some babies born with a predisposition to become anxious? Questions about individual differences in temperament have engaged the minds of scientists, psychologists, and philosophers for centuries. Recent technological advances in neuroimaging and genetics provide an unprecedented opportunity to answer these questions. Here we review the literature on the neurobiology of one of the most basic individual differences—the tendency to approach or avoid novelty. This trait, called inhibited temperament, is innate, heritable, and observed across species. Importantly, inhibited temperament also confers risk for psychiatric disease. Here, we provide a comprehensive review of inhibited temperament including neuroimaging and genetic studies in human and non-human primates. We conducted a meta-analysis of neuroimaging findings in inhibited humans that points to alterations in a fronto-limbic-basal ganglia circuit; these findings provide the basis of a model of inhibited temperament neurocircuitry. Lesion and neuroimaging studies in non-human primate models of inhibited temperament highlight roles for the amygdala, hippocampus, orbitofrontal cortex, and dorsal prefrontal cortex. Genetic studies highlight a role for genes that regulate neurotransmitter function, such as the serotonin transporter polymorphisms (5-HTTLPR), as well as genes that regulate stress response, such as corticotropin-releasing hormone (CRH). Together these studies provide a foundation of knowledge about the genetic and neural substrates of this most basic of temperament traits. Future studies using novel imaging methods and genetic approaches promise to expand upon these biological bases of inhibited temperament and inform our understanding of risk for psychiatric disease. PMID:25784645

The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis.

PubMed

Clauss, J A; Avery, S N; Blackford, J U

2015-04-01

What makes us different from one another? Why does one person jump out of airplanes for fun while another prefers to stay home and read? Why are some babies born with a predisposition to become anxious? Questions about individual differences in temperament have engaged the minds of scientists, psychologists, and philosophers for centuries. Recent technological advances in neuroimaging and genetics provide an unprecedented opportunity to answer these questions. Here we review the literature on the neurobiology of one of the most basic individual differences-the tendency to approach or avoid novelty. This trait, called inhibited temperament, is innate, heritable, and observed across species. Importantly, inhibited temperament also confers risk for psychiatric disease. Here, we provide a comprehensive review of inhibited temperament, including neuroimaging and genetic studies in human and non-human primates. We conducted a meta-analysis of neuroimaging findings in inhibited humans that points to alterations in a fronto-limbic-basal ganglia circuit; these findings provide the basis of a model of inhibited temperament neurocircuitry. Lesion and neuroimaging studies in non-human primate models of inhibited temperament highlight roles for the amygdala, hippocampus, orbitofrontal cortex, and dorsal prefrontal cortex. Genetic studies highlight a role for genes that regulate neurotransmitter function, such as the serotonin transporter polymorphisms (5-HTTLPR), as well as genes that regulate stress response, such as corticotropin-releasing hormone (CRH). Together these studies provide a foundation of knowledge about the genetic and neural substrates of this most basic of temperament traits. Future studies using novel imaging methods and genetic approaches promise to expand upon these biological bases of inhibited temperament and inform our understanding of risk for psychiatric disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Back to the Basics: Cnidarians Start to Fire

PubMed Central

Bosch, Thomas C. G.; Klimovich, Alexander; Domazet-Lošo, Tomislav; Gründer, Stefan; Holstein, Thomas W.; Jékely, Gáspár; Miller, David J.; Murillo-Rincon, Andrea P.; Rentzsch, Fabian; Richards, Gemma S.; Schröder, Katja; Technau, Ulrich; Yuste, Rafael

2016-01-01

The nervous systems of cnidarians, pre-bilaterian animals that diverged close to the base of the metazoan radiation, are structurally simple and thus have great potential to inform us about basic structural and functional principles of neural circuits. Unfortunately, cnidarians have thus far been relatively intractable to electrophysiological and genetic techniques and consequently have been largely passed over by neurobiologists. However, recent advances in molecular and imaging methods are fueling a renaissance of interest in and research into cnidarians nervous systems. Here, we review current knowledge on the nervous systems of some cnidarian species and propose that researchers should seize this opportunity and undertake the study of this phylum as strategic experimental systems with great basic and translational relevance for neuroscience. PMID:28041633

Complete nucleotide sequence of the Oenothera elata plastid chromosome, representing plastome I of the five distinguishable euoenothera plastomes.

PubMed

Hupfer, H; Swiatek, M; Hornung, S; Herrmann, R G; Maier, R M; Chiu, W L; Sears, B

2000-05-01

We describe the 159,443-bp [corrected] sequence of the plastid chromosome of Oenothera elata (evening primrose). The Oe. elata plastid chromosome represents type I of the five genetically distinguishable basic plastomes found in the subsection Euoenothera. The genus Oenothera provides an ideal system in which to address fundamental questions regarding the functional integration of the compartmentalised genetic system characteristic of the eukaryotic cell. Its highly developed taxonomy and genetics, together with a favourable combination of features in its genetic structure (interspecific fertility, stable heterozygous progeny, biparental transmission of organelles, and the phenomenon of complex heterozygosity), allow facile exchanges of nuclei, plastids and mitochondria, as well as individual chromosome pairs, between species. The resulting hybrids or cybrids are usually viable and fertile, but can display various forms of developmental disturbance.

Myriad Genetics: In the eye of the policy storm

PubMed Central

Gold, E. Richard; Carbone, Julia

2011-01-01

From the late 1980s, a storm surrounding the wisdom, ethics, and economics of human gene patents has been brewing. The various winds of concern in this storm touched on the impact of gene patents on basic and clinical research, on health care delivery, and on the ability of public health care systems to provide equal access when faced with costly patented genetic diagnostic tests. Myriad Genetics, Inc., along with its subsidiary, Myriad Genetic Laboratories, Inc., a small Utah-based biotechnology company, found itself unwittingly in the eye of this storm after a series of decisions it made regarding the commercialization of a hereditary breast cancer diagnostic test. This case study examine the background to Myriad's decisions, the context in which these decisions were made and the policy, research and business response to them. PMID:20393310

Use of Contemporary Genetics in Cardiovascular Diagnosis

PubMed Central

George, Alfred L.

2015-01-01

An explosion of knowledge regarding the genetic and genomic basis for rare and common diseases has provided a framework for revolutionizing the practice of medicine. Achieving the reality of a genomic medicine era requires that basic discoveries are effectively translated into clinical practice through implementation of genetic and genomic testing. Clinical genetic tests have become routine for many inherited disorders and can be regarded as the standard-of-care in many circumstances including disorders affecting the cardiovascular system. New, high-throughput methods for determining the DNA sequence of all coding exons or complete genomes are being adopted for clinical use to expand the speed and breadth of genetic testing. Along with these extraordinary advances have emerged new challenges to practicing physicians for understanding when and how to use genetic testing along with how to appropriately interpret test results. This review will acquaint readers with general principles of genetic testing including newer technologies, test interpretation and pitfalls. The focus will be on testing genes responsible for monogenic disorders and on other emerging applications such as pharmacogenomic profiling. The discussion will be extended to the new paradigm of direct-to-consumer genetic testing and the value of assessing genomic risk for common diseases. PMID:25421045

Maintenance of genetic variation in human personality: Testing evolutionary models by estimating heritability due to common causal variants and investigating the effect of distant inbreeding

PubMed Central

Verweij, Karin J.H.; Yang, Jian; Lahti, Jari; Veijola, Juha; Hintsanen, Mirka; Pulkki-Råback, Laura; Heinonen, Kati; Pouta, Anneli; Pesonen, Anu-Katriina; Widen, Elisabeth; Taanila, Anja; Isohanni, Matti; Miettunen, Jouko; Palotie, Aarno; Penke, Lars; Service, Susan K.; Heath, Andrew C.; Montgomery, Grant W.; Raitakari, Olli; Kähönen, Mika; Viikari, Jorma; Räikkönen, Katri; Eriksson, Johan G; Keltikangas-Järvinen, Liisa; Lehtimäki, Terho; Martin, Nicholas G.; Järvelin, Marjo-Riitta; Visscher, Peter M.; Keller, Matthew C.; Zietsch, Brendan P.

2012-01-01

Personality traits are basic dimensions of behavioural variation, and twin, family, and adoption studies show that around 30% of the between-individual variation is due to genetic variation. There is rapidly-growing interest in understanding the evolutionary basis of this genetic variation. Several evolutionary mechanisms could explain how genetic variation is maintained in traits, and each of these makes predictions in terms of the relative contribution of rare and common genetic variants to personality variation, the magnitude of nonadditive genetic influences, and whether personality is affected by inbreeding. Using genome-wide SNP data from >8,000 individuals, we estimated that little variation in the Cloninger personality dimensions (7.2% on average) is due to the combined effect of common, additive genetic variants across the genome, suggesting that most heritable variation in personality is due to rare variant effects and/or a combination of dominance and epistasis. Furthermore, higher levels of inbreeding were associated with less socially-desirable personality trait levels in three of the four personality dimensions. These findings are consistent with genetic variation in personality traits having been maintained by mutation-selection balance. PMID:23025612

Histological Features of Methylene Blue-Induced Phototoxicity Administered in the Context of Parathyroid Surgery.

PubMed

Maguire, Ciara A; Sharma, Anup; Alarcon, Lida; Ffolkes, Lorrette; Kurzepa, Malgorzata; Ostlere, Lucy; Samarasinghe, Venura; Singh, Manuraj

2017-08-01

Methylene blue is a chromophore dye known for its photosensitizing properties. It is also administered intravenously as a tracer in parathyroid surgery to identify abnormal glands. We describe 2 cases of acute methylene blue-induced phototoxicity in patients who underwent parathyroidectomy. Both patients developed an acute vesiculopustular inflammatory rash on the anterior neck corresponding to the site exposed intraoperatively to overhanging surgical lights. One of the patients also developed a bulla on her finger at the site of attachment of the oxygen probe. Biopsies were taken from both patients at different time points. The histological findings included destruction of sebaceous glands and deposition of diastase-periodic acid-Schiff-positive hyaline material around dermal blood vessels. These features are similar to those seen in skin treated with photodynamic therapy and systemic photosensitivity disorders such as the porphyrias. The wavelengths of light emitted by the surgical lights and oxygen probe overlap with the absorption spectrum of methylene blue. This resulted in excitation of the systemically administered methylene blue at exposed sites, with resultant local tissue damage and a phototoxic reaction.

[Postoperative cognitive deficits].

PubMed

Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

2006-01-01

Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

Conference summary: Navigating the Sea of Genomic Data, October 28-29, 2015.

PubMed

Pihlstrom, Bruce L; Barnett, Michael L

2016-03-01

The rapid pace of biomedical discoveries in the past few years has resulted in substantial advances in our ability to diagnose, treat, and prevent a wide variety of diseases. The sequencing of the human genome offered the possibility of understanding the etiology, pathogenesis, and risk of developing disease from a genetic perspective and has resulted, for example, in the development of genomic-based diagnostic or risk-assessment tests for a number of medical and dental conditions. To assess the scientific evidence underlying such tests and determine whether they may be useful in clinical practice, practitioners need to have a basic understanding of the state-of-the-science of genomics and genetic testing. To assist practitioners in understanding the science of genomics, the American Dental Association and the Task Force on Design and Analysis in Oral Health Research co-sponsored a landmark conference, Navigating the Sea of Genomic Data, held October 28-29, 2015, at the American Dental Association headquarters building in Chicago, IL. The purpose of this conference was to review the basics of genomic science, promote sound design and analysis of genomic studies of oral diseases, and provide a basis or "framework" to guide practitioners in assessing new development in genomics and genetic tests for oral diseases. Presentations at this conference were made by 9 world-renowned scientists who discussed a wide range of topics involving genomic science, genetic testing for rare mendelian single gene disorders, and genetic testing for assessing the risk of experiencing common complex diseases. This article summarizes the key points and concepts presented by the speakers. It is essential for oral health care professionals to have a fundamental understanding of genomic science so that they can evaluate new advances in this field and the use of genetic testing for the benefit of their patients. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

The complete nucleotide sequences of the five genetically distinct plastid genomes of Oenothera, subsection Oenothera: I. sequence evaluation and plastome evolution.

PubMed

Greiner, Stephan; Wang, Xi; Rauwolf, Uwe; Silber, Martina V; Mayer, Klaus; Meurer, Jörg; Haberer, Georg; Herrmann, Reinhold G

2008-04-01

The flowering plant genus Oenothera is uniquely suited for studying molecular mechanisms of speciation. It assembles an intriguing combination of genetic features, including permanent translocation heterozygosity, biparental transmission of plastids, and a general interfertility of well-defined species. This allows an exchange of plastids and nuclei between species often resulting in plastome-genome incompatibility. For evaluation of its molecular determinants we present the complete nucleotide sequences of the five basic, genetically distinguishable plastid chromosomes of subsection Oenothera (=Euoenothera) of the genus, which are associated in distinct combinations with six basic genomes. Sizes of the chromosomes range from 163 365 bp (plastome IV) to 165 728 bp (plastome I), display between 96.3% and 98.6% sequence similarity and encode a total of 113 unique genes. Plastome diversification is caused by an abundance of nucleotide substitutions, small insertions, deletions and repetitions. The five plastomes deviate from the general ancestral design of plastid chromosomes of vascular plants by a subsection-specific 56 kb inversion within the large single-copy segment. This inversion disrupted operon structures and predates the divergence of the subsection presumably 1 My ago. Phylogenetic relationships suggest plastomes I-III in one clade, while plastome IV appears to be closest to the common ancestor.

The complete nucleotide sequences of the five genetically distinct plastid genomes of Oenothera, subsection Oenothera: I. Sequence evaluation and plastome evolution†

PubMed Central

Greiner, Stephan; Wang, Xi; Rauwolf, Uwe; Silber, Martina V.; Mayer, Klaus; Meurer, Jörg; Haberer, Georg; Herrmann, Reinhold G.

2008-01-01

The flowering plant genus Oenothera is uniquely suited for studying molecular mechanisms of speciation. It assembles an intriguing combination of genetic features, including permanent translocation heterozygosity, biparental transmission of plastids, and a general interfertility of well-defined species. This allows an exchange of plastids and nuclei between species often resulting in plastome–genome incompatibility. For evaluation of its molecular determinants we present the complete nucleotide sequences of the five basic, genetically distinguishable plastid chromosomes of subsection Oenothera (=Euoenothera) of the genus, which are associated in distinct combinations with six basic genomes. Sizes of the chromosomes range from 163 365 bp (plastome IV) to 165 728 bp (plastome I), display between 96.3% and 98.6% sequence similarity and encode a total of 113 unique genes. Plastome diversification is caused by an abundance of nucleotide substitutions, small insertions, deletions and repetitions. The five plastomes deviate from the general ancestral design of plastid chromosomes of vascular plants by a subsection-specific 56 kb inversion within the large single-copy segment. This inversion disrupted operon structures and predates the divergence of the subsection presumably 1 My ago. Phylogenetic relationships suggest plastomes I–III in one clade, while plastome IV appears to be closest to the common ancestor. PMID:18299283

The value of the study of natural history in genetic disorders and congenital anomaly syndromes.

PubMed Central

Hall, J G

1988-01-01

The study of the natural history of genetic disorders and syndromes with congenital anomalies and dysmorphic features is a challenging and often neglected area. There are many reasons to pursue this type of research but it requires special clinical skills and a considerable amount of hard work. Setting up protocols and collecting data is complex and time consuming. Frequently, helpful clues for a particular disorder come from the study of the natural history of other disorders. Older affected subjects and unique cases with unusual features are often most important in unravelling the 'normal' course of a disease or recognising the basic defect. The study of natural history from individual patients and their records is complementary to population or registry based studies because it identifies individual variations and clinical heterogeneity. The understanding of the natural history of a particular disorder is of importance both to the affected person and their family and to the physicians caring for them. It is also useful to the basic researcher trying to determine the pathogenetic mechanism causing the disorder. In many ways, clinical geneticists have learned the art of caring for patients, as well as the challenges of clinical genetics, by becoming apprentices to and studying in depth specific disease entities. PMID:3050091

Basic Concepts in Molecular Biology Related to Genetics and Epigenetics.

PubMed

Corella, Dolores; Ordovas, Jose M

2017-09-01

The observation that "one size does not fit all" for the prevention and treatment of cardiovascular disease, among other diseases, has driven the concept of precision medicine. The goal of precision medicine is to provide the best-targeted interventions tailored to an individual's genome. The human genome is composed of billions of sequence arrangements containing a code that controls how genes are expressed. This code depends on other nonstatic regulators that surround the DNA and constitute the epigenome. Moreover, environmental factors also play an important role in this complex regulation. This review provides a general perspective on the basic concepts of molecular biology related to genetics and epigenetics and a glossary of key terms. Several examples are given of polymorphisms and genetic risk scores related to cardiovascular risk. Likewise, an overview is presented of the main epigenetic regulators, including DNA methylation, methylcytosine-phosphate-guanine-binding proteins, histone modifications, other histone regulations, micro-RNA effects, and additional emerging regulators. One of the greatest challenges is to understand how environmental factors (diet, physical activity, smoking, etc.) could alter the epigenome, resulting in healthy or unhealthy cardiovascular phenotypes. We discuss some gene-environment interactions and provide a methodological overview. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

A Transparent Window into Biology: A Primer on Caenorhabditis elegans.

PubMed

Corsi, Ann K; Wightman, Bruce; Chalfie, Martin

2015-06-01

A little over 50 years ago, Sydney Brenner had the foresight to develop the nematode (round worm) Caenorhabditis elegans as a genetic model for understanding questions of developmental biology and neurobiology. Over time, research on C. elegans has expanded to explore a wealth of diverse areas in modern biology including studies of the basic functions and interactions of eukaryotic cells, host-parasite interactions, and evolution. C. elegans has also become an important organism in which to study processes that go awry in human diseases. This primer introduces the organism and the many features that make it an outstanding experimental system, including its small size, rapid life cycle, transparency, and well-annotated genome. We survey the basic anatomical features, common technical approaches, and important discoveries in C. elegans research. Key to studying C. elegans has been the ability to address biological problems genetically, using both forward and reverse genetics, both at the level of the entire organism and at the level of the single, identified cell. These possibilities make C. elegans useful not only in research laboratories, but also in the classroom where it can be used to excite students who actually can see what is happening inside live cells and tissues. Copyright © 2015 Corsi, Wightman, and Chalfie.

Peptide aptamers: The versatile role of specific protein function inhibitors in plant biotechnology.

PubMed

Colombo, Monica; Mizzotti, Chiara; Masiero, Simona; Kater, Martin M; Pesaresi, Paolo

2015-11-01

In recent years, peptide aptamers have emerged as novel molecular tools that have attracted the attention of researchers in various fields of basic and applied science, ranging from medicine to analytical chemistry. These artificial short peptides are able to specifically bind, track, and inhibit a given target molecule with high affinity, even molecules with poor immunogenicity or high toxicity, and represent a remarkable alternative to antibodies in many different applications. Their use is on the rise, driven mainly by the medical and pharmaceutical sector. Here we discuss the enormous potential of peptide aptamers in both basic and applied aspects of plant biotechnology and food safety. The different peptide aptamer selection methods available both in vivo and in vitro are introduced, and the most important possible applications in plant biotechnology are illustrated. In particular, we discuss the generation of broad-based virus resistance in crops, "reverse genetics" and aptasensors in bioassays for detecting contaminations in food and feed. Furthermore, we suggest an alternative to the transfer of peptide aptamers into plant cells via genetic transformation, based on the use of cell-penetrating peptides that overcome the limits imposed by both crop transformation and Genetically Modified Organism commercialization. © 2015 Institute of Botany, Chinese Academy of Sciences.

Expanding the species and chemical diversity of Penicillium section Cinnamopurpurea

USDA-ARS?s Scientific Manuscript database

A set of isolates genetically similar to or potentially conspecific with an unidentified Penicillium isolate NRRL 735, was assembled using a Basic Local Alignment Search Tool (BLAST) search of internal transcribed spacer (ITS) similarity among described (GenBank) and undescribed Penicillium isolates...

Specific Syndromes and Associated Communication Disorders: A Review.

ERIC Educational Resources Information Center

Sanger, Dixie D.; And Others

1984-01-01

The review, intended to provide speech-language pathologists and special educators with an awareness of genetics and specific syndromes involving speech, language, and hearing components, discusses basic etiologies of abnormal development and selected syndromes (such as Down's and Klinefelter's) that include communication disorders. (CL)

Clover, Red (Trifolium pretense)

USDA-ARS?s Scientific Manuscript database

Genetic modification of plants by the insertion of transgenes can be a powerful experimental approach to answer basic questions about gene product function. This technology can also be used to make improved crop varieties for use in the field. To apply this powerful tool to red clover, an important ...

75 FR 26970 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

...-496-8551, [email protected] . Name of Committee: Molecular, Cellular and Developmental...: Oncology 1--Basic Translational Integrated Review Group, Cancer Genetics Study Section. Date: June 3-4... 20892, (301) 435-1154, [email protected] . Name of Committee: Molecular, Cellular and Developmental...

The double life of DNA

PubMed Central

McMurray, Cynthia T.; Vijg, Jan

2015-01-01

This issue of Current Opinions focuses on the dual role of DNA in life and death. In ancient Roman religion and myth, Janus is the god who looks both to the past and to the future. He guides the beginnings of life, its progression from one condition to another, and he foresees distant events. The analogy to DNA could not be stronger. Closely interacting with the environment, our basic genetics provides the origin of life, guides the quality of health with age, predicts disease, and ultimately foresees our end. A shared and deep interest in the origin of life has long prompted our desire to define aging, and, ultimately, to understand whether it can be reversed. In this special issue, the authors collectively review concepts of normative aging, DNA instability, DNA repair, the genetic contribution of age and diet to disease, and how the basic molecular transactions of DNA give it a double life that guides health and survival, as well as the transitions to death. PMID:25282314

Precision medicine and drug development in Alzheimer's disease: The importance of sexual dimorphism and patient stratification.

PubMed

Hampel, Harald; Vergallo, Andrea; Giorgi, Filippo Sean; Kim, Seung Hyun; Depypere, Herman; Graziani, Manuela; Saidi, Amira; Nisticò, Robert; Lista, Simone

2018-06-12

Neurodegenerative diseases (ND) are among the leading causes of disability and mortality. Considerable sex differences exist in the occurrence of the various manifestations leading to cognitive decline. Alzheimer's disease (AD) exhibits substantial sexual dimorphisms and disproportionately affects women. Women have a higher life expectancy compared to men and, consequently, have more lifespan to develop AD. The emerging precision medicine and pharmacology concepts - taking into account the individual genetic and biological variability relevant for disease risk, prevention, detection, diagnosis, and treatment - are expected to substantially enhance our knowledge and management of AD. Stratifying the affected individuals by sex and gender is an important basic step towards personalization of scientific research, drug development, and care. We hypothesize that sex and gender differences, extending from genetic to psychosocial domains, are highly relevant for the understanding of AD pathophysiology, and for the conceptualization of basic/translational research and for clinical therapy trial design. Copyright © 2018 Elsevier Inc. All rights reserved.

Holistic Nursing in the Genetic/Genomic Era.

PubMed

Sharoff, Leighsa

2016-06-01

Holistic nursing practice is an ever-evolving transformative process with core values that require continued growth, professional leadership, and advocacy. Holistic nurses are required to stay current with all new required competencies, such as the Core Competencies in Genetics for Health Professional, and, as such, be adept at translating scientific evidence relating to genetics/genomics in the clinical setting. Knowledge of genetics/genomics in relation to nursing practice, policy, utilization, and research influence nurses' responsibilities. In addition to holistic nursing competencies, the holistic nurse must have basic knowledge and skills to integrate genetics/genomics aspects. It is important for holistic nurses to enhance their overall knowledge foundation, skills, and attitudes about genetics to prepare for the transformation in health care that is already underway. Holistic nurses can provide an important perspective to the application of genetics and genomics, focusing on health promotion, caring, and understanding the relationship between caring and families, community, and society. Yet there may be a lack of genetic and genomic knowledge to fully participate in the current genomic era. This article will explore the required core competencies for all health care professionals, share linkage of holistic nurses in practice with genetic/genomic conditions, and provide resources to further one's knowledge base. © The Author(s) 2015.

Genetic testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS joint statement.

PubMed

Vlahovich, Nicole; Hughes, David C; Griffiths, Lyn R; Wang, Guan; Pitsiladis, Yannis P; Pigozzi, Fabio; Bachl, Nobert; Eynon, Nir

2017-11-14

There has been considerable growth in basic knowledge and understanding of how genes are influencing response to exercise training and predisposition to injuries and chronic diseases. On the basis of this knowledge, clinical genetic tests may in the future allow the personalisation and optimisation of physical activity, thus providing an avenue for increased efficiency of exercise prescription for health and disease. This review provides an overview of the current status of genetic testing for the purposes of exercise prescription and injury prevention. As such there are a variety of potential uses for genetic testing, including identification of risks associated with participation in sport and understanding individual response to particular types of exercise. However, there are many challenges remaining before genetic testing has evidence-based practical applications; including adoption of international standards for genomics research, as well as resistance against the agendas driven by direct-to-consumer genetic testing companies. Here we propose a way forward to develop an evidence-based approach to support genetic testing for exercise prescription and injury prevention. Based on current knowledge, there is no current clinical application for genetic testing in the area of exercise prescription and injury prevention, however the necessary steps are outlined for the development of evidence-based clinical applications involving genetic testing.

Genetics/genomics education for nongenetic health professionals: a systematic literature review.

PubMed

Talwar, Divya; Tseng, Tung-Sung; Foster, Margaret; Xu, Lei; Chen, Lei-Shih

2017-07-01

The completion of the Human Genome Project has enhanced avenues for disease prevention, diagnosis, and management. Owing to the shortage of genetic professionals, genetics/genomics training has been provided to nongenetic health professionals for years to establish their genomic competencies. We conducted a systematic literature review to summarize and evaluate the existing genetics/genomics education programs for nongenetic health professionals. Five electronic databases were searched from January 1990 to June 2016. Forty-four studies met our inclusion criteria. There was a growing publication trend. Program participants were mainly physicians and nurses. The curricula, which were most commonly provided face to face, included basic genetics; applied genetics/genomics; ethical, legal, and social implications of genetics/genomics; and/or genomic competencies/recommendations in particular professional fields. Only one-third of the curricula were theory-based. The majority of studies adopted a pre-/post-test design and lacked follow-up data collection. Nearly all studies reported participants' improvements in one or more of the following areas: knowledge, attitudes, skills, intention, self-efficacy, comfort level, and practice. However, most studies did not report participants' age, ethnicity, years of clinical practice, data validity, and data reliability. Many genetics/genomics education programs for nongenetic health professionals exist. Nevertheless, enhancement in methodological quality is needed to strengthen education initiatives.Genet Med advance online publication 20 October 2016.

Inbred or Outbred? Genetic Diversity in Laboratory Rodent Colonies

PubMed Central

Brekke, Thomas D.; Steele, Katherine A.; Mulley, John F.

2017-01-01

Nonmodel rodents are widely used as subjects for both basic and applied biological research, but the genetic diversity of the study individuals is rarely quantified. University-housed colonies tend to be small and subject to founder effects and genetic drift; so they may be highly inbred or show substantial genetic divergence from other colonies, even those derived from the same source. Disregard for the levels of genetic diversity in an animal colony may result in a failure to replicate results if a different colony is used to repeat an experiment, as different colonies may have fixed alternative variants. Here we use high throughput sequencing to demonstrate genetic divergence in three isolated colonies of Mongolian gerbil (Meriones unguiculatus) even though they were all established recently from the same source. We also show that genetic diversity in allegedly “outbred” colonies of nonmodel rodents (gerbils, hamsters, house mice, deer mice, and rats) varies considerably from nearly no segregating diversity to very high levels of polymorphism. We conclude that genetic divergence in isolated colonies may play an important role in the “replication crisis.” In a more positive light, divergent rodent colonies represent an opportunity to leverage genetically distinct individuals in genetic crossing experiments. In sum, awareness of the genetic diversity of an animal colony is paramount as it allows researchers to properly replicate experiments and also to capitalize on other genetically distinct individuals to explore the genetic basis of a trait. PMID:29242387

Genetic Determinism in the Genetics Curriculum. An Exploratory Study of the Effects of Mendelian and Weldonian Emphases

NASA Astrophysics Data System (ADS)

Jamieson, Annie; Radick, Gregory

2017-12-01

Twenty-first-century biology rejects genetic determinism, yet an exaggerated view of the power of genes in the making of bodies and minds remains a problem. What accounts for such tenacity? This article reports an exploratory study suggesting that the common reliance on Mendelian examples and concepts at the start of teaching in basic genetics is an eliminable source of support for determinism. Undergraduate students who attended a standard `Mendelian approach' university course in introductory genetics on average showed no change in their determinist views about genes. By contrast, students who attended an alternative course which, inspired by the work of a critic of early Mendelism, W. F. R. Weldon (1860-1906), replaced an emphasis on Mendel's peas with an emphasis on developmental contexts and their role in bringing about phenotypic variability, were less determinist about genes by the end of teaching. Improvements in both the new Weldonian curriculum and the study design are in view for the future.

Genetic architecture of retinal and macular degenerative diseases: the promise and challenges of next-generation sequencing

PubMed Central

2013-01-01

Inherited retinal degenerative diseases (RDDs) display wide variation in their mode of inheritance, underlying genetic defects, age of onset, and phenotypic severity. Molecular mechanisms have not been delineated for many retinal diseases, and treatment options are limited. In most instances, genotype-phenotype correlations have not been elucidated because of extensive clinical and genetic heterogeneity. Next-generation sequencing (NGS) methods, including exome, genome, transcriptome and epigenome sequencing, provide novel avenues towards achieving comprehensive understanding of the genetic architecture of RDDs. Whole-exome sequencing (WES) has already revealed several new RDD genes, whereas RNA-Seq and ChIP-Seq analyses are expected to uncover novel aspects of gene regulation and biological networks that are involved in retinal development, aging and disease. In this review, we focus on the genetic characterization of retinal and macular degeneration using NGS technology and discuss the basic framework for further investigations. We also examine the challenges of NGS application in clinical diagnosis and management. PMID:24112618

Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

PubMed Central

Yuan, Yanfang; Xu, Wentao; He, Xiaoyun; Liu, Haiyan; Cao, Sishuo; Qi, Xiaozhe; Huang, Kunlun; Luo, Yunbo

2013-01-01

Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health. PMID:23752350

Genetic Incorporation of Twelve meta-Substituted Phenylalanine Derivatives Using A Single Pyrrolysyl-tRNA Synthetase

PubMed Central

Wang, Yane-Shih; Fang, Xinqiang; Chen, Hsueh-Ying; Wu, Bo; Wang, Zhiyong U.; Hilty, Christian; Liu, Wenshe R.

2012-01-01

When coexpressed with its cognate amber suppressing tRNACUAPyl, a pyrrolysyl-tRNA synthetase mutant N346A/C348A is able to genetically incorporate twelve meta-substituted phenylalanine derivatives into proteins site-specifically at amber mutation sites in Escherichia coli. These genetically encoded noncanonical amino acids resemble phenylalanine in size and contain diverse bioorthogonal functional groups such as halide, trifluoromethyl, nitrile, nitro, ketone, alkyne, and azide moieties. The genetic installation of these functional groups in proteins provides multiple ways to site-selectively label proteins with biophysical and biochemical probes for their functional investigations. We demonstrate that a genetically incorporated trifluoromethyl group can be used as a sensitive 19F NMR probe to study protein folding/unfolding, and that genetically incorporated reactive functional groups such as ketone, alkyne, and azide moieties can be applied to site-specifically label proteins with florescent probes. This critical discovery allows the synthesis of proteins with diverse bioorthogonal functional groups for a variety of basic studies and biotechnology development using a single recombinant expression system. PMID:23138887

Genetic variation among the Golla pastoral caste subdivisions of Andhra Pradesh, India, according to the HLA system.

PubMed

Crawford, M H; Reddy, B M; Martinez-Laso, J; Mack, S J; Erlich, H A

2001-09-01

The HLA allele frequency distributions have been characterized for the HLA class I and class II loci of the Golla pastoral caste, from Southeast India, subdivided into the subcastes (Puja, Punugu, Kurava, Pokanati, Karnam, and Doddi). Genetic distances, neighbor-joining, correspondence, and haplotype analyses all indicate that the subcastes exhibit a high haplotype variability and that their genetic substratum may be the result of European-Middle East/Asian admixture with the autochthonous populations. The Karnam subcaste seems to be the one that has undergone a higher degree of admixture, when compared with the other subcastes. The Golla speak an old Indian Dravidian language and should theoretically represent the basic Indian substratum that existed before the postulated "Aryan" invasion.

Future Translational Applications From the Contemporary Genomics Era

PubMed Central

Fox, Caroline S.; Hall, Jennifer L.; Arnett, Donna K.; Ashley, Euan A.; Delles, Christian; Engler, Mary B.; Freeman, Mason W.; Johnson, Julie A.; Lanfear, David E.; Liggett, Stephen B.; Lusis, Aldons J.; Loscalzo, Joseph; MacRae, Calum A.; Musunuru, Kiran; Newby, L. Kristin; O’Donnell, Christopher J.; Rich, Stephen S.; Terzic, Andre

2016-01-01

The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care. PMID:25882488

On the Optimization of Aerospace Plane Ascent Trajectory

NASA Astrophysics Data System (ADS)

Al-Garni, Ahmed; Kassem, Ayman Hamdy

A hybrid heuristic optimization technique based on genetic algorithms and particle swarm optimization has been developed and tested for trajectory optimization problems with multi-constraints and a multi-objective cost function. The technique is used to calculate control settings for two types for ascending trajectories (constant dynamic pressure and minimum-fuel-minimum-heat) for a two-dimensional model of an aerospace plane. A thorough statistical analysis is done on the hybrid technique to make comparisons with both basic genetic algorithms and particle swarm optimization techniques with respect to convergence and execution time. Genetic algorithm optimization showed better execution time performance while particle swarm optimization showed better convergence performance. The hybrid optimization technique, benefiting from both techniques, showed superior robust performance compromising convergence trends and execution time.

Tilting at Quixotic Trait Loci (QTL): An Evolutionary Perspective on Genetic Causation

PubMed Central

Weiss, Kenneth M.

2008-01-01

Recent years have seen great advances in generating and analyzing data to identify the genetic architecture of biological traits. Human disease has understandably received intense research focus, and the genes responsible for most Mendelian diseases have successfully been identified. However, the same advances have shown a consistent if less satisfying pattern, in which complex traits are affected by variation in large numbers of genes, most of which have individually minor or statistically elusive effects, leaving the bulk of genetic etiology unaccounted for. This pattern applies to diverse and unrelated traits, not just disease, in basically all species, and is consistent with evolutionary expectations, raising challenging questions about the best way to approach and understand biological complexity. PMID:18711218

PhyloGeoViz: a web-based program that visualizes genetic data on maps.

PubMed

Tsai, Yi-Hsin E

2011-05-01

The first step of many population genetic studies is the simple visualization of allele frequencies on a landscape. This basic data exploration can be challenging without proprietary software, and the manual plotting of data is cumbersome and unfeasible at large sample sizes. I present an open source, web-based program that plots any kind of frequency or count data as pie charts in Google Maps (Google Inc., Mountain View, CA). Pie polygons are then exportable to Google Earth (Google Inc.), a free Geographic Information Systems platform. Import of genetic data into Google Earth allows phylogeographers access to a wealth of spatial information layers integral to forming hypotheses and understanding patterns in the data. © 2010 Blackwell Publishing Ltd.

Molecular basis of angiosperm tree architecture.

PubMed

Hollender, Courtney A; Dardick, Chris

2015-04-01

The architecture of trees greatly impacts the productivity of orchards and forestry plantations. Amassing greater knowledge on the molecular genetics that underlie tree form can benefit these industries, as well as contribute to basic knowledge of plant developmental biology. This review describes the fundamental components of branch architecture, a prominent aspect of tree structure, as well as genetic and hormonal influences inferred from studies in model plant systems and from trees with non-standard architectures. The bulk of the molecular and genetic data described here is from studies of fruit trees and poplar, as these species have been the primary subjects of investigation in this field of science. No claim to original US Government works. New Phytologist © 2014 New Phytologist Trust.

Breeding design considerations for coastal Douglas-fir.

Treesearch

Randy Johnson

1998-01-01

The basic principles of designing forest tree breeding programs are reviewed for Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) in the Pacific Northwest. Breeding populations are discussed given current and future breeding zone sizes and seed orchard designs. Seed orchard composition is discussed for potential genetic gain and maintaining...

Teaching Cell Division: Basics and Recommendations.

ERIC Educational Resources Information Center

Smith, Mike U.; Kindfield, Ann C. H.

1999-01-01

Presents a concise overview of cell division that includes only the essential concepts necessary for understanding genetics and evolution. Makes recommendations based on published research and teaching experiences that can be used to judge the merits of potential activities and materials for teaching cell division. Makes suggestions regarding the…

Are High School Students Prepared for a Brave New World?

ERIC Educational Resources Information Center

Blake, Deborah

1984-01-01

Describes Notre Dame High School's (California) integrated bioethics course, which contains units on basic concepts of goals, rights, and duty ethics; reproductive technologies; genetic technologies; death and dying; behavior modification; and experiments with human subjects. Provides a bibliography of student and teacher materials. (DMM)

78 FR 60296 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

... 20892, 301-435-1501, [email protected] . Name of Committee: Genes, Genomes, and Genetics Integrated Review Group; Prokaryotic Cell and Molecular Biology Study Section. Date: October 25, 2013. Time: 8:00 a... Committee: Oncology 1-Basic Translational Integrated Review Group; Cancer Molecular Pathobiology Study...

Diversity and history as drivers of helminth systematics and biology

USDA-ARS?s Scientific Manuscript database

Systematics is the foundation for biology. It provides a basic evolutionary map to discover, characterize and interpret global diversity and our place in the biosphere. It also allows us to explore questions related to host associations, life history, genetics, and patterns of infection and disease,...

The Molecular Basis of Development.

ERIC Educational Resources Information Center

Gehring, Walter J.

1985-01-01

Basic architecture of embryo development appears to be under homeobox control (a short stretch of DNA). Outlines research on this genetic segment in fruit flies which led to identification of this control on the embryo's spatial organization. Indicates that molecular mechanisms underlying development may be much more universal than previously…

The Contribution of Buckwheat Genetic Resources to Health and Dietary Diversity

PubMed Central

Sytar, Oksana; Brestic, Marian; Zivcak, Marek; Tran, Lam-Son Phan

2016-01-01

Despite several reports on the beneficial effects of buckwheat in prevention of human diseases, little attention has been devoted to the variability of biochemical and physiological traits in different buckwheat genetic resources. This review describes the biochemical evaluation of buckwheat genetic resources and the identification of elite genotypes for plant breeding and exploitation. The various types of bioactive compounds present in different varieties provide basic background information needed for the efficient production of buckwheat foods with added value. In this review, we will provide an integrated view of the biochemistry of bioactive compounds of buckwheat plants of different origin, especially of fagopyrin, proteins and amino acids, as well as of other phenolic compounds including rutin and chlorogenic acid. In addition to the genetic background, the effect of different growth conditions is discussed. The health effects of fagopyrin, phenolic acids, specific proteins and rutin are also presented. PMID:27252586

Medical genetics, public understanding and patient experiences: An exploratory qualitative study of recently pregnant women

NASA Astrophysics Data System (ADS)

Garman, Jamie L.

The purpose of the study was to document how individuals' experiences and understanding of genetics concepts affects their medical experiences. Recently pregnant women were interviewed because they represent a population that needs to comprehend biological and genetic information to understand their health. Three women were designated as science experts (SE) defined as having extensive university level science education and three women were designated as science non-experts (SNE). In general, SEs described a more positive pregnancy experience. Both SEs and SNEs demonstrated a basic understanding of genetic concepts but varied in the application of concepts to personal medical issues. Participants' views and experiences of pre and postnatal tests were linked to their understanding of nature of science components such as recognition that tests have limitations. Results from this study indicate an incomplete understanding of the nature of science among participants may have led to unsatisfactory medical experiences.

Rapid identification of kidney cyst mutations by whole exome sequencing in zebrafish

PubMed Central

Ryan, Sean; Willer, Jason; Marjoram, Lindsay; Bagwell, Jennifer; Mankiewicz, Jamie; Leshchiner, Ignaty; Goessling, Wolfram; Bagnat, Michel; Katsanis, Nicholas

2013-01-01

Forward genetic approaches in zebrafish have provided invaluable information about developmental processes. However, the relative difficulty of mapping and isolating mutations has limited the number of new genetic screens. Recent improvements in the annotation of the zebrafish genome coupled to a reduction in sequencing costs prompted the development of whole genome and RNA sequencing approaches for gene discovery. Here we describe a whole exome sequencing (WES) approach that allows rapid and cost-effective identification of mutations. We used our WES methodology to isolate four mutations that cause kidney cysts; we identified novel alleles in two ciliary genes as well as two novel mutants. The WES approach described here does not require specialized infrastructure or training and is therefore widely accessible. This methodology should thus help facilitate genetic screens and expedite the identification of mutants that can inform basic biological processes and the causality of genetic disorders in humans. PMID:24130329

Plasmids for increased efficiency of vector construction and genetic engineering in filamentous fungi.

PubMed

Schoberle, Taylor J; Nguyen-Coleman, C Kim; May, Gregory S

2013-01-01

Fungal species are continuously being studied to not only understand disease in humans and plants but also to identify novel antibiotics and other metabolites of industrial importance. Genetic manipulations, such as gene deletion, gene complementation, and gene over-expression, are common techniques to investigate fungal gene functions. Although advances in transformation efficiency and promoter usage have improved genetic studies, some basic steps in vector construction are still laborious and time-consuming. Gateway cloning technology solves this problem by increasing the efficiency of vector construction through the use of λ phage integrase proteins and att recombination sites. We developed a series of Gateway-compatible vectors for use in genetic studies in a range of fungal species. They contain nutritional and drug-resistance markers and can be utilized to manipulate different filamentous fungal genomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Sleep and Development in Genetically Tractable Model Organisms.

PubMed

Kayser, Matthew S; Biron, David

2016-05-01

Sleep is widely recognized as essential, but without a clear singular function. Inadequate sleep impairs cognition, metabolism, immune function, and many other processes. Work in genetic model systems has greatly expanded our understanding of basic sleep neurobiology as well as introduced new concepts for why we sleep. Among these is an idea with its roots in human work nearly 50 years old: sleep in early life is crucial for normal brain maturation. Nearly all known species that sleep do so more while immature, and this increased sleep coincides with a period of exuberant synaptogenesis and massive neural circuit remodeling. Adequate sleep also appears critical for normal neurodevelopmental progression. This article describes recent findings regarding molecular and circuit mechanisms of sleep, with a focus on development and the insights garnered from models amenable to detailed genetic analyses. Copyright © 2016 by the Genetics Society of America.

Analysis of the basic science section of the orthopaedic in-training examination.

PubMed

Sheibani-Rad, Shahin; Arnoczky, Steven Paul; Walter, Norman E

2012-08-01

Since 1963, the Orthopaedic In-Training Examination (OITE) has been administered to orthopedic residents to assess residents' knowledge and measure the quality of teaching within individual programs. The OITE currently consists of 275 questions divided among 12 domains. This study analyzed all OITE basic science questions between 2006 and 2010. The following data were recorded: number of questions, question taxonomy, category of question, type of imaging modality, and recommended journal and book references. Between 2006 and 2010, the basic science section constituted 12.2% of the OITE. The assessment of taxonomy classification showed that recall-type questions were the most common, at 81.4%. Imaging modalities typically involved questions on radiographs and constituted 6.2% of the OITE basic science section. The majority of questions were basic science questions (eg, genetics, cell replication, and bone metabolism), with an average of 26.4 questions per year. The Journal of Bone & Joint Surgery (American Volume) and the American Academy of Orthopaedic Surgeons' Orthopaedic Basic Science were the most commonly and consistently cited journal and review book, respectively. This study provides the first review of the question content and recommended references of the OITE basic science section. This information will provide orthopedic trainees, orthopedic residency programs, and the American Academy of Orthopaedic Surgeons Evaluation Committee valuable information related to improving residents' knowledge and performance and optimizing basic science educational curricula. Copyright 2012, SLACK Incorporated.

Strong Genetic Overlap Between Executive Functions and Intelligence

PubMed Central

Engelhardt, Laura E.; Mann, Frank D.; Briley, Daniel A.; Church, Jessica A.; Harden, K. Paige; Tucker-Drob, Elliot M.

2016-01-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision-making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7-15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically-mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. PMID:27359131

Synthesizing genetic sequential logic circuit with clock pulse generator.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

Education Status of Oral Genetics at the Fourth Military Medical University and other Chinese Dental Schools.

PubMed

Zhang, Yan Li; Wang, Chang Ning; Fan, Zhi Peng; Jiao, Yang; Duan, Xiao Hong

To investigate the current state of genetics education at the Fourth Military Medical University (FMMU) and compare it with other dental schools of China. Detailed information about the history and current education status of Oral Genetics in the FMMU were collected and questionnaires were completed to acquire the feedback of twenty-seven students on the course. In the other thirty-five dental schools including the capitals of twenty-five provinces and four municipalities in China, information about the oral genetic course were collected by a telephone survey. The contents of survey included whether or not the Oral Genetic course is offered and some basic information about the curriculum (such as the content, hours, teachers' background and teaching methods). Among a total of thirty-six dental schools investigated, six of them (16.7%) offered the Oral Genetic course or related lectures/seminars. The length and contents of the curriculum vary among these schools. The FMMU offered the oral genetic curriculum both to undergraduates and graduated students. Their teachers had a broad range of backgrounds, such as dentistry, biology, genetics, and biochemistry. The students considered the Oral Genetics course to be helpful for their future professional careers. Genetic education in dentistry in China is still at a preliminary stage. More effort must be paid to spread the knowledge of Oral Genetics in China. In addition, domestic and international communications and networks for Oral Genetics should be set up in the near future.

A Comparison of Telephone Genetic Counseling and In-Person Genetic Counseling from the Genetic Counselor's Perspective.

PubMed

Burgess, Kelly R; Carmany, Erin P; Trepanier, Angela M

2016-02-01

Growing demand for and limited geographic access to genetic counseling services is increasing the need for alternative service delivery models (SDM) like telephone genetic counseling (TGC). Little research has been done on genetic counselors' perspectives of the practice of TGC. We created an anonymous online survey to assess whether telephone genetic counselors believed the tasks identified in the ABGC (American Board of Genetic Counseling) Practice Analysis were performed similarly or differently in TGC compared to in person genetic counseling (IPGC). If there were differences noted, we sought to determine the nature of the differences and if additional training might be needed to address them. Eighty eight genetic counselors with experience in TGC completed some or all of the survey. Respondents identified differences in 13 (14.8%) of the 88 tasks studied. The tasks identified as most different in TGC were: "establishing rapport through verbal and nonverbal interactions" (60.2%; 50/83 respondents identified the task as different), "recognizing factors affecting the counseling interaction" (47.8%; 32/67), "assessing client/family emotions, support, etc." (40.1%; 27/66) and "educating clients about basic genetic concepts" (35.6%; 26/73). A slight majority (53.8%; 35/65) felt additional training was needed to communicate information without visual aids and more effectively perform psychosocial assessments. In summary, although a majority of genetic counseling tasks are performed similarly between TGC and IPGC, TGC counselors recognize that specific training in the TGC model may be needed to address the key differences.

Malaria Evolution in South Asia: Knowledge for Control and Elimination

PubMed Central

Narayanasamy, Krishnamoorthy; Chery, Laura; Basu, Analabha; Duraisingh, Manoj T.; Escalante, Ananias; Fowble, Joseph; Guler, Jennifer L.; Herricks, Thurston; Kumar, Ashwani; Majumder, Partha; Maki, Jennifer; Mascarenhas, Anjali; Rodrigues, Janneth; Roy, Bikram; Sen, Somdutta; Shastri, Jayanthi; Smith, Joseph; Valecha, Neena; White, John; Rathod, Pradipsinh K.

2013-01-01

The study of malaria parasites on the Indian subcontinent should help us understand unexpected disease outbreaks and unpredictable disease presentations from Plasmodium falciparum and from Plasmodium vivax infections. The Malaria Evolution in South Asia (MESA) research program is one of ten International Centers of Excellence for Malaria Research (ICEMR) sponsored by the US National Institute of Health. In this second of two reviews, we describe why population structures of Plasmodia in India will be characterized and how we will determine their consequences on disease presentation, outcome and patterns. Specific projects will determine if genetic diversity, possibly driven by parasites with higher genetic plasticity, plays a role in changing epidemiology, pathogenesis, vector competence of parasite populations, and whether innate human genetic traits protect Indians from malaria today. Deep local clinical knowledge of malaria in India will be supplemented by basic scientists who bring new research tools. Such tools will include whole genome sequencing and analysis methods; in vitro assays to measure genome plasticity, RBC cytoadhesion, invasion, and deformability; mosquito infectivity assays to evaluate changing parasite-vector compatibilities; and host genetics to understand protective traits in Indian populations. The MESA-ICEMR study sites span diagonally across India, including a mixture of very urban and rural hospitals, each with very different disease patterns and patient populations. Research partnerships include government-associated research institutes, private medical schools, city and state government hospitals, and hospitals with industry ties. Between 2012-2017, in addition to developing clinical research and basic science infrastructure at new clinical sites, our training workshops will engage new scientists and clinicians throughout South Asia in the malaria research field. PMID:22266213

The updated experimental proteinoid model

NASA Technical Reports Server (NTRS)

Fox, S. W.; Nakashima, T.; Przybylski, A.; Syren, R. M.

1982-01-01

The experimental proteinoid model includes new results indicating that polymers sufficiently rich in basic amino acid catalyze the synthesis of peptides from ATP and amino acids and of oligonucleotides from ATP. The need for simulation syntheses of amino acids yielding significant proportions of basic amino acids is now in focus. The modeled simultaneous protocellular synthesis of peptides and polynucleotides is part of a more comprehensive proposal for the origin of the coded genetic mechanism. The finding of membrane and action potentials in proteinoid microspheres, with or without added lecithin, is reported. The crucial nature of a nonrandom matrix for protocells is developed.

Biotechnology in the High School Classroom.

ERIC Educational Resources Information Center

Ahmed, Maryam

1996-01-01

Describes a project that introduces students to the field of biotechnology and provides them with an understanding of the basic principles and techniques as well as an opportunity to participate in experimental methodology. Presents specific science projects that deal with polymorphism in the lipase gene and the genetic engineering of a lipase…

Sex Differences in Mental and Behavioral Traits.

ERIC Educational Resources Information Center

Garai, Josef E.; Scheinfeld, Amram

1968-01-01

This review of research conducted on sex differences attempts to answer the following questions: (1) Do the sexes differ in their basic capacities for specific types of mental performance and occupational achievement? (2) If such differences exist, to what extent are they genetically determined? (3) Are sex differences in abilities, interests, and…

Characteristics of the USA dairy herd as related to management and demographic elements

USDA-ARS?s Scientific Manuscript database

The data characteristics of the United States dairy herd related to animals enrolled in milk recording (dairy herd improvement) are the basic foundation and important influencers for the management and genetic progress achieved in a population or animal production unit. The amount, characteristics ...

Are the Major Agglutinative Languages Genetically Related?

ERIC Educational Resources Information Center

Hakola, H. P. A.

1989-01-01

Examination of accidental CVC and CV correspondences among languages representing 5 large families of agglutinative languages found that comparison pairs had much more similarity between basic 100-word vocabularies than would have been possible by mere chance, supporting the hypothesis that those 5 language families were mutually related.…

Variation in height growth and growth

Treesearch

Knud E. Clausen

1968-01-01

Yellow birch (Betula alleghaniensis Britt.) is an important hardwood species in the Lake States, northeastern United States, and eastern Canada. Since it produces valuable timber, the species is a logical candidate for genetic improvement. An understanding of the variation pattern in a species is, however, basic to any improvement program. In 1963...

THE MENTALLY RETARDED.

ERIC Educational Resources Information Center

JORDAN, THOMAS E.

THIS BOOK PROVIDES A GUIDE TO THE BASIC CONCEPTS AND ISSUES IN THE FIELD OF MENTAL RETARDATION. THERE ARE MANY SOURCES OR CAUSES OF MENTAL RETARDATION AND THE FOLLOWING TYPES ARE EXPLAINED--(1) GENETIC OR CHEMICAL DISORDERS, (2) BIRTH TRAUMA, (3) SUBSEQUENT ACCIDENTS OR DISEASE, AND (4) ENVIRONMENTAL INFLUENCES. IT IS NOTED THAT MOST CASES INVOLVE…

BASIC Simulation Programs; Volumes I and II. Biology, Earth Science, Chemistry.

ERIC Educational Resources Information Center

Digital Equipment Corp., Maynard, MA.

Computer programs which teach concepts and processes related to biology, earth science, and chemistry are presented. The seven biology problems deal with aspects of genetics, evolution and natural selection, gametogenesis, enzymes, photosynthesis, and the transport of material across a membrane. Four earth science problems concern climates, the…

Bioethics in the Hunger Games

ERIC Educational Resources Information Center

Cook, Kristin; Keller, Donna; Myers, Alyce

2014-01-01

In this guided inquiry, students investigate advantages and disadvantages of genetic engineering by integrating popular fiction into their study of bioethics. What are the effects of artificially created hybrid creatures on characters in "The Hunger Games" and in our society? What are the effects on and basic rights of the organisms…

Deciphering maize genetics and ecology to reduce insect damage and aflatoxin accumulation

USDA-ARS?s Scientific Manuscript database

Ear-colonizing insects and diseases, which reduce yield and impose health threats via mycotoxin contaminations, are critical impediments for maize production in the southern US states. To address this problem a combination of basic and applied research approaches are being conducted by the interdis...

MaizeGDB: enabling access to basic, translational, and applied research information

USDA-ARS?s Scientific Manuscript database

MaizeGDB is the Maize Genetics and Genomics Database (available online at http://www.maizegdb.org). The MaizeGDB project is not simply an online database and website but rather an information service to maize researchers that supports customized data access and analysis needs to individual research...

Vico's Theory of Knowledge and Some Problems in Genetic Epistemology.

ERIC Educational Resources Information Center

Gash, Hugh

1983-01-01

Argues that Vico's constructivist epistemology is germane to contemporary cognitive developmental psychology, first in clarifying the meaning of the environment in Piaget's theory and second by providing, through the description of mental operations, a way of overcoming directions to the overly formal quality of Piaget's basic concrete-operational…

Phonological Awareness and Reading in Boys with Fragile X Syndrome

ERIC Educational Resources Information Center

Adlof, Suzanne M.; Klusek, Jessica; Shinkareva, Svetlana V.; Robinson, Marissa L.; Roberts, Jane E.

2015-01-01

Background: Reading delays are well documented in children with fragile X syndrome (FXS), but few studies have examined linguistic precursors of reading in this population. This study examined the longitudinal development of phonological awareness and its relationship with basic reading in boys with FXS. Individual differences in genetic,…

Collection of wild Helianthus anomalus and deserticola sunflower from the desert southwest USA

USDA-ARS?s Scientific Manuscript database

Genetic resources are the biological basis of global food security. Collection and preservation of wild relatives of important crop species such as sunflower provide the basic foundation to improve and sustain the crop. Acquisition through exploration is the initial step in the germplasm conservatio...

An Instructional Approach to Modeling in Microevolution.

ERIC Educational Resources Information Center

Thompson, Steven R.

1988-01-01

Describes an approach to teaching population genetics and evolution and some of the ways models can be used to enhance understanding of the processes being studied. Discusses the instructional plan, and the use of models including utility programs and analysis with models. Provided are a basic program and sample program outputs. (CW)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalousek, D.K.; Fitch, N.; Paradice, B.

Topics covered in this book include a general review of normal embryonic and fetal development; abortion and the basic approach to the examination of aborted embryos and fetuses; and pathologic findings detected on examination of products of conception. The authors illustrate specific morphologic lesions and the variable expression of genetic syndromes in the embryonic and fetal periods.

What Does Culture Have to Do with Teaching Science?

ERIC Educational Resources Information Center

Madden, Lauren; Joshi, Arti

2013-01-01

In nearly every elementary school, plants are an important part of the science curriculum. Understanding basic ideas about plants prepares children to study more complicated scientific concepts including cell biology, genetics and heredity, complex ecosystem interactions, and evolution. It is especially important that teachers of children at the…

Seth M. Noone | NREL

Science.gov Websites

Education M.S., Biomedical Basic Science, Department of Biochemistry and Molecular Genetics, University of Interaction with Histones H3 and H4," Molecular and Cellular Biology (2013) "The Lysine 48 and Cerevisiae," Molecular and Cellular Biology (2007) View all NREL Publications for Seth M. Noone

Independent Gene Discovery and Testing

ERIC Educational Resources Information Center

Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

2010-01-01

A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

Epilepsy; A Review of Basic and Clinical Research. NINDB Monograph Number 1.

ERIC Educational Resources Information Center

Robb, Preston

A discussion of the incidence of epilepsy is followed by a discussion of etiology including the following causes: genetic and birth factors, infectious diseases, toxic factors, trauma or physical agents, heredofamilial and degenerative disorders, circulatory disturbances, metabolic and nutritional disturbances, and neoplasms. Epileptic seizures…

Role of Genomic Typing in Taxonomy, Evolutionary Genetics, and Microbial Epidemiology

PubMed Central

van Belkum, Alex; Struelens, Marc; de Visser, Arjan; Verbrugh, Henri; Tibayrenc, Michel

2001-01-01

Currently, genetic typing of microorganisms is widely used in several major fields of microbiological research. Taxonomy, research aimed at elucidation of evolutionary dynamics or phylogenetic relationships, population genetics of microorganisms, and microbial epidemiology all rely on genetic typing data for discrimination between genotypes. Apart from being an essential component of these fundamental sciences, microbial typing clearly affects several areas of applied microbiogical research. The epidemiological investigation of outbreaks of infectious diseases and the measurement of genetic diversity in relation to relevant biological properties such as pathogenicity, drug resistance, and biodegradation capacities are obvious examples. The diversity among nucleic acid molecules provides the basic information for all fields described above. However, researchers in various disciplines tend to use different vocabularies, a wide variety of different experimental methods to monitor genetic variation, and sometimes widely differing modes of data processing and interpretation. The aim of the present review is to summarize the technological and fundamental concepts used in microbial taxonomy, evolutionary genetics, and epidemiology. Information on the nomenclature used in the different fields of research is provided, descriptions of the diverse genetic typing procedures are presented, and examples of both conceptual and technological research developments for Escherichia coli are included. Recommendations for unification of the different fields through standardization of laboratory techniques are made. PMID:11432813

DOE Office of Scientific and Technical Information (OSTI.GOV)

McEwen, J.E.; McCarty, K.; Reilly, P.R.

Rapid advances in the ability to test persons presymptomatically for genetic diseases have generated increasing concern that genetic information will be abused by insurance companies. Reasoning that the insurance companies may have the strongest interest in using genetic data and that the medical directors of those companies with responsibility for rating applicants would be a good source of information on the use of such data, the authors conducted a large survey of medical directors of North American life insurance companies. They received responses from 27 medical directors. The results suggest that (1) few insurers perform genetic tests on applicants, butmore » most are interested in accessing genetic test information about applicants that already exists; (2) the degree of insurers' interest in using genetic test results may depend on the face amount of the policy applied for and on the specificity and sensitivity of the test; (3) many companies employ underwriting guidelines with respect to certain genetic conditions but may not always have specific actuarial data in house to support their rating decisions; (4) a considerable degree of subjectivity is involved in most insurers' rating decisions; and (5) some of the medical directors who responded to the survey are not fully informed about certain basic principles of medical genetics. 8 refs., 7 tabs.« less

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.

PubMed

Fang, Qing; George, Akima S; Brinkmeier, Michelle L; Mortensen, Amanda H; Gergics, Peter; Cheung, Leonard Y M; Daly, Alexandre Z; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A Bilge; Kitzman, Jacob O; Mills, Ryan E; Li, Jun Z; Camper, Sally A

2016-12-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD.

Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes.

PubMed

Marchegiani, Shannon; Davis, Taylor; Tessadori, Federico; van Haaften, Gijs; Brancati, Francesco; Hoischen, Alexander; Huang, Haigen; Valkanas, Elise; Pusey, Barbara; Schanze, Denny; Venselaar, Hanka; Vulto-van Silfhout, Anneke T; Wolfe, Lynne A; Tifft, Cynthia J; Zerfas, Patricia M; Zambruno, Giovanna; Kariminejad, Ariana; Sabbagh-Kermani, Farahnaz; Lee, Janice; Tsokos, Maria G; Lee, Chyi-Chia R; Ferraz, Victor; da Silva, Eduarda Morgana; Stevens, Cathy A; Roche, Nathalie; Bartsch, Oliver; Farndon, Peter; Bermejo-Sanchez, Eva; Brooks, Brian P; Maduro, Valerie; Dallapiccola, Bruno; Ramos, Feliciano J; Chung, Hon-Yin Brian; Le Caignec, Cédric; Martins, Fabiana; Jacyk, Witold K; Mazzanti, Laura; Brunner, Han G; Bakkers, Jeroen; Lin, Shuo; Malicdan, May Christine V; Boerkoel, Cornelius F; Gahl, William A; de Vries, Bert B A; van Haelst, Mieke M; Zenker, Martin; Markello, Thomas C

2015-07-02

Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

“I Didn’t Know It Existed Before You Called”: Protestant Clergy Experience, Education and Perceptions Regarding Genetics

PubMed Central

Ragsdale, Judy; Vaughn, Lisa; Grossoehme, Daniel

2015-01-01

Despite the intrinsic role religious/spiritual (hereafter, R/S) beliefs have in patient clinical decision-making and crisis coping, there is little research exploring the relationship that exists between clergy (professionals who provide R/S counsel and guidance) and genetic counseling patients. This qualitative, exploratory study was designed to explore Protestant clergy (N=8) perceptions of and experience with genetics-related issues. Data analysis revealed that a wide range of R/S perceptions regarding genetics-related issues exist within Protestantism, Protestant clergy have a basic understanding of genetic testing and conditions, and while directive counseling is inherent to Protestant clergy counseling, there appears to exist two opposing styles: unbiased and biased. Based on this information, there are two main implications for genetic counseling clinical practice. First, R/S assessments need to be increasingly implemented into genetic counseling sessions, so that the psychosocial needs of patients with specific R/S beliefs can be identified and addressed. An increase in R/S assessments may be accomplished by increased exposure in genetic counselor training, continuing education opportunities, and by establishing relationships with board-certified, professional chaplains. Second, genetic counselors can influence the genetic education and experience of clergy by raising awareness within their own R/S assemblies. Doing so can also serve to further educate genetic counselors in the R/S beliefs of their own traditions, thus increasing sensitivity, empathy and the quality of care provided. PMID:23054334

Elephant behaviour and conservation: social relationships, the effects of poaching, and genetic tools for management.

PubMed

Archie, Elizabeth A; Chiyo, Patrick I

2012-02-01

Genetic tools are increasingly valuable for understanding the behaviour, evolution, and conservation of social species. In African elephants, for instance, genetic data provide basic information on the population genetic causes and consequences of social behaviour, and how human activities alter elephants' social and genetic structures. As such, African elephants provide a useful case study to understand the relationships between social behaviour and population genetic structure in a conservation framework. Here, we review three areas where genetic methods have made important contributions to elephant behavioural ecology and conservation: (1) understanding kin-based relationships in females and the effects of poaching on the adaptive value of elephant relationships, (2) understanding patterns of paternity in elephants and how poaching can alter these patterns, and (3) conservation genetic tools to census elusive populations, track ivory, and understand the behavioural ecology of crop-raiding. By comparing studies from populations that have experienced a range of poaching intensities, we find that human activities have a large effect on elephant behaviour and genetic structure. Poaching disrupts kin-based association patterns, decreases the quality of elephant social relationships, and increases male reproductive skew, with important consequences for population health and the maintenance of genetic diversity. In addition, we find that genetic tools to census populations or gather forensic information are almost always more accurate than non-genetic alternatives. These results contribute to a growing understanding of poaching on animal behaviour, and how genetic tools can be used to understand and conserve social species. © 2011 Blackwell Publishing Ltd.

Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease.

PubMed

McKibbin, Martin; Ahmed, Mushtaq; Allsop, Matthew J; Downey, Louise; Gale, Richard; Grant, Hilary Louise; Potrata, Barbara; Willis, Thomas A; Hewison, Jenny

2014-09-01

Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations.

Genetics and Genomics of Endometriosis

PubMed Central

Hansen, Keith A.; Eyster, Kathleen M.

2015-01-01

Endometriosis is a common cause of morbidity in women with an unknown etiology. Studies have demonstrated the familial nature of endometriosis and suggest that inheritance occurs in a polygenic/multifactorial fashion. Studies have attempted to define the gene or genes responsible for endometriosis through association or linkage studies with candidate genes or DNA mapping technology. A number of genomics studies have demonstrated significant alterations in gene expression in endometriosis. A more thorough understanding of the genetics and genomics of endometriosis will facilitate understanding the basic biology of the disease and open new inroads to diagnosis and treatment of this enigmatic condition. PMID:20436317

On Gene Concepts and Teaching Genetics: Episodes from Classical Genetics

NASA Astrophysics Data System (ADS)

Burian, Richard M.

2013-02-01

This paper addresses the teaching of advanced high school courses or undergraduate courses for non-biology majors about genetics or history of genetics. It will probably be difficult to take the approach described here in a high school science course, although the general approach could help improve such courses. It would be ideal for a college course in history of genetics or a course designed to teach non-science majors how science works or the rudiments of the genetics in a way that will help them as citizens. The approach aims to teach the processes of discovery, correction, and validation by utilizing illustrative episodes from the history of genetics. The episodes are treated in way that should foster understanding of basic questions about genes, the sorts of techniques used to answer questions about the constitution and structure of genes, how they function, and what they determine, and some of the major biological disagreements that arose in dealing with these questions. The material covered here could be connected to social and political issues raised by genetics, but these connections are not surveyed here. As it is, to cover this much territory, the article is limited to four major episodes from Mendel's paper to the beginning of World War II. A sequel will deal with the molecularization of genetics and with molecular gene concepts through the Human Genome Project.

Forensic and population genetic characteristics of 62 X chromosome SNPs revealed by multiplex PCR and MALDI-TOF mass spectrometry genotyping in 4 North Eurasian populations.

PubMed

Stepanov, Vadim; Vagaitseva, Ksenyia; Kharkov, Vladimir; Cherednichenko, Anastasia; Bocharova, Anna; Berezina, Galina; Svyatova, Gulnara

2016-01-01

X chromosome genetic markers are widely used in basic population genetic research as well as in forensic genetics. In this paper we analyze the genetic diversity of 62 X chromosome SNPs in 4 populations using multiplex genotyping based on multi-locus PCR and MALDI-TOF mass spectrometry, and report forensic and population genetic features of the panel of X-linked SNPs (XSNPid). Studied populations represent Siberian (Buryat and Khakas), North Asian (Khanty) and Central Asian (Kazakh) native people. Khanty, Khakas and Kazakh population demonstrate average gene diversity over 0.45. Only East Siberian Buryat population is characterized by lower average heterozygosity (0.436). AMOVA analysis of genetic structure reveals a relatively low but significant level of genetic differentiation in a group of 4 population studied (FST=0.023, p=0.0000). The XSNPid panel provides a very high discriminating power in each population. The combined probability of discrimination in females (PDf) for XSNPid panel ranged between populations from 0.99999999999999999999999982 in Khakas to 0.9999999999999999999999963 in Buryats. The combined discriminating power in males (PDm) varies from 0.999999999999999792 to 0.9999999999999999819. The developed multiplex set of X chromosome SNPs can be a useful tool for population genetic studies and for forensic identity and kinship testing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Distinguishing genetics and eugenics on the basis of fairness.

PubMed Central

Ledley, F D

1994-01-01

There is concern that human applications of modern genetic technologies may lead inexorably to eugenic abuse. To prevent such abuse, it is essential to have clear, formal principles as well as algorithms for distinguishing genetics from eugenics. This work identifies essential distinctions between eugenics and genetics in the implied nature of the social contract and the importance ascribed to individual welfare relative to society. Rawls's construction of 'justice as fairness' is used as a model for how a formal systems of ethics can be used to proscribe eugenic practices. Rawls's synthesis can be applied to this problem if it is assumed that in the original condition all individuals are ignorant of their genetic constitution and unwilling to consent to social structures which may constrain their own potential. The principles of fairness applied to genetics requires that genetic interventions be directed at extending individual liberties and be applied to the greatest benefit of individuals with the least advantages. These principles are incompatible with negative eugenics which would further penalize those with genetic disadvantage. These principles limit positive eugenics to those practices which are designed to provide absolute benefit to those individuals with least advantage, are acceptable to its subjects, and further a system of basic equal liberties. This analysis also illustrates how simple deviations from first principles in Rawls's formulation could countenance eugenic applications of genetic technologies. PMID:7996561

Cardiovascular pharmacogenetics: a promise for genomically-guided therapy and personalized medicine.

PubMed

Zaiou, M; El Amri, H

2017-03-01

Cardiovascular disease (CVD) is the leading cause of death worldwide. The basic causes of CVD are not fully understood yet. Substantial evidence suggests that genetic predisposition plays a vital role in the physiopathology of this complex disease. Hence, identification of genetic contributors to CVD will likely add diagnostic accuracy and better prediction of an individual's risk. With high-throughput genetics and genomics technology and newer genome-wide study approaches, a number of genetic variations across the human genome were uncovered. Evidence suggests that genetic defects could influence CVD development and inter-individual responses to widely used cardiovascular drugs like clopidogrel, aspirin, warfarin, and statins, and therefore, they may be integrated into clinical practice. If clinically validated, better understanding of these genetic variations may provide new opportunities for personalized diagnostic, pharmacogenetic-based drug selection and best treatment in personalized medicine. However, numerous gaps remain unsolved due to the lack of underlying pathological mechanisms for how genetic predisposition could contribute to CVD. This review provides an overview of the extraordinary scientific progress in our understanding of genetic and genomic basis of CVD as well as the development of relevant genetic biomarkers for this disease. Some of the actual limitations to the promise of these markers and their translation for the benefit of patients will be discussed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Looking forward in geriatric anxiety and depression: implications of basic science for the future.

PubMed

Gershenfeld, Howard K; Philibert, Robert A; Boehm, Gary W

2005-12-01

Major depression and anxiety are common psychiatric illnesses whose etiology remains incompletely understood. This review highlights progress in understanding the etiology of these illnesses through genetic strategies and looks forward to their impact on geriatric psychiatry. We briefly address three broad domains of progress, namely 1) genetic approaches to etiology, including linkage and association studies, pharmacogenetics ("personalized medicine"), and gene x environment interactions; 2) mechanisms of thyroid and testosterone action via nuclear receptors, given these hormones' status as possible augmenters of antidepressants; and 3) the role of the neuroimmune system as a contributor to the stress response. Genetic strategies offer one path for converting correlational findings into causal pathways while complementing studies of a gene's function at the molecular, cellular, network, and whole-organismal levels. Neuroendocrine supplementation (thyroid and testosterone) has a long history and tradition. A molecular understanding of nuclear receptor pathways and their coactivators, the mediator complex proteins, provides a rationale for improved targeting of hormonal action in a tissue-selective manner, yielding drugs with improved safety and efficacy. Neural-immune interactions in psychiatric illness remain tantalizing topics. Research suggests that cytokine pathways may contribute to the maintenance or susceptibility to stress, anxiety, and depressive disorders. The reciprocal and recursive interactions among basic science, drug discovery, and clinical science will continue to provide hopeful themes for improving the lives of patients with treatment-refractive psychiatric illness.

The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model­

PubMed Central

VandenBroeke, Marie; Youn, Jiun; Ellenbroek, Arabella K.; Karel, Peter; Shan, Ling; van Boxtel, Ruben; Ooms, Sharon; Balemans, Monique; Langedijk, Jacqueline; Muller, Mareike; Vriend, Gert; Cools, Alexander R.; Cuppen, Edwin; Ellenbroek, Bart A.

2016-01-01

ABSTRACT Social cognition is an endophenotype that is impaired in schizophrenia and several other (comorbid) psychiatric disorders. One of the modulators of social cognition is dopamine, but its role is not clear. The effects of dopamine are mediated through dopamine receptors, including the dopamine D1 receptor (Drd1). Because current Drd1 receptor agonists are not Drd1 selective, pharmacological tools are not sufficient to delineate the role of the Drd1. Here, we describe a novel rat model with a genetic mutation in Drd1 in which we measured basic behavioural phenotypes and social cognition. The I116S mutation was predicted to render the receptor less stable. In line with this computational prediction, this Drd1 mutation led to a decreased transmembrane insertion of Drd1, whereas Drd1 expression, as measured by Drd1 mRNA levels, remained unaffected. Owing to decreased transmembrane Drd1 insertion, the mutant rats displayed normal basic motoric and neurological parameters, as well as locomotor activity and anxiety-like behaviour. However, measures of social cognition like social interaction, scent marking, pup ultrasonic vocalizations and sociability, were strongly reduced in the mutant rats. This profile of the Drd1 mutant rat offers the field of neuroscience a novel genetic rat model to study a series of psychiatric disorders including schizophrenia, autism, depression, bipolar disorder and drug addiction. PMID:27483345

Recurrent evolution of life history ecotypes in sockeye salmon: implications for conservation and future evolution

PubMed Central

Wood, Chris C; Bickham, John W; John Nelson, R; Foote, Chris J; Patton, John C

2008-01-01

We examine the evolutionary history and speculate about the evolutionary future of three basic life history ecotypes that contribute to the biocomplexity of sockeye salmon (Oncorhynchus nerka). The ‘recurrent evolution’ (RE) hypothesis claims that the sea/river ecotype is ancestral, a ‘straying’ form with poorly differentiated (meta)population structure, and that highly structured populations of lake-type sockeye and kokanee have evolved repeatedly in parallel adaptive radiations between recurrent glaciations of the Pleistocene Epoch. Basic premises of this hypothesis are consistent with new, independent evidence from recent surveys of genetic variation in mitochondrial and microsatellite DNA: (1) sockeye salmon are most closely related to pink (O. gorbuscha) and chum (O. keta) salmon with sea-type life histories; (2) the sockeye life history ecotypes exist as polyphyletic lineages within large drainages and geographic regions; (3) the sea/river ecotype exhibits less genetic differentiation among populations than the lake or kokanee ecotypes both within and among drainages; and (4) genetic diversity is typically higher in the sea/river ecotype than in the lake and kokanee ecotypes. Anthropogenic modification of estuarine habitat and intensive coastal fisheries have likely reduced and fragmented historic metapopulations of the sea/river ecotype, particularly in southern areas. In contrast, the kokanee ecotype appears to be favoured by marine fisheries and predicted changes in climate. PMID:25567627

Research Associate | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) at the Frederick National Laboratory for Cancer Research (FNLCR) pursues independent, multidisciplinary research programs in basic or applied molecular biology, immunology, retrovirology, cancer biology or human genetics. As part of the BSP, the Microbiome and Genetics Core (the Core) characterizes microbiomes by next-generation sequencing to determine their composition and variation, as influenced by immune, genetic, and host health factors. The Core provides support across a spectrum of processes, from nucleic acid isolation through bioinformatics and statistical analysis. KEY ROLES/RESPONSIBILITIES The Research Associate II will provide support in the areas of automated isolation, preparation, PCR and sequencing of DNA on next generation platforms (Illumina MiSeq and NextSeq). An opportunity exists to join the Core’s team of highly trained experimentalists and bioinformaticians working to characterize microbiome samples. The following represent requirements of the position: A minimum of five (5) years related of biomedical experience. Experience with high-throughput nucleic acid (DNA/RNA) extraction. Experience in performing PCR amplification (including quantitative real-time PCR). Experience or familiarity with robotic liquid handling protocols (especially on the Eppendorf epMotion 5073 or 5075 platforms). Experience in operating and maintaining benchtop Illumina sequencers (MiSeq and NextSeq). Ability to evaluate experimental quality and to troubleshoot molecular biology protocols. Experience with sample tracking, inventory management and biobanking. Ability to operate and communicate effectively in a team-oriented work environment.

The human sweet tooth.

PubMed

Reed, Danielle R; McDaniel, Amanda H

2006-06-15

Humans love the taste of sugar and the word "sweet" is used to describe not only this basic taste quality but also something that is desirable or pleasurable, e.g., la dolce vita. Although sugar or sweetened foods are generally among the most preferred choices, not everyone likes sugar, especially at high concentrations. The focus of my group's research is to understand why some people have a sweet tooth and others do not. We have used genetic and molecular techniques in humans, rats, mice, cats and primates to understand the origins of sweet taste perception. Our studies demonstrate that there are two sweet receptor genes (TAS1R2 and TAS1R3), and alleles of one of the two genes predict the avidity with which some mammals drink sweet solutions. We also find a relationship between sweet and bitter perception. Children who are genetically more sensitive to bitter compounds report that very sweet solutions are more pleasant and they prefer sweet carbonated beverages more than milk, relative to less bitter-sensitive peers. Overall, people differ in their ability to perceive the basic tastes, and particular constellations of genes and experience may drive some people, but not others, toward a caries-inducing sweet diet. Future studies will be designed to understand how a genetic preference for sweet food and drink might contribute to the development of dental caries.

Basic-education mexican teachers' knowledge of biotechnology and attitudes about the consumption of genetically modified foods.

PubMed

Jiménez-Salas, Zacarías; Campos-Góngora, Eduardo; González-Martínez, Blanca E; Tijerina-Sáenz, Alexandra; Escamilla-Méndez, Angélica D; Ramírez-López, Erik

2017-09-01

Over the past few years, a new research field has emerged, focusing on the social-scientific criteria for the study of opinions toward genetically modified foods (GMFs), since these may be limiting factors for the success or failure of these products. Basic education is the first step in the Mexican education system, and teachers may wield an outsized influence on the attitudes and preferences of children, prospective future consumers of these products. To better understand the current state of knowledge of biotechnology issues and opinions toward the consumption of GMF of Mexican teachers, a questionnaire was distributed, and 362 Mexican teachers of basic education responded. The survey included questions about the benefits and risks of consuming GMF. The mean percentage of teachers expressing knowledge of a given topic in biotechnology was 50%. More than 60% of teachers believed that GMFs would be useful in preventing world hunger, while 39.2% considered GMF to be hazards for future generations. Although 47.0% reported not having enough knowledge about these topics, almost all (90.3%) respondents expressed an interest and willingness to learn about biotechnology. In light of the fact that teachers of basic education represent the first and potentially most lasting stage in the education of young children, this survey establishes the urgent need to develop strategies to improve the scientific knowledge of teachers and to facilitate decision making and the promotion of scientific and technological advances for their students. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):396-402, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Critical Need for Family-Based, Quasi-Experimental Designs in Integrating Genetic and Social Science Research

PubMed Central

Lahey, Benjamin B.; Turkheimer, Eric; Lichtenstein, Paul

2013-01-01

Researchers have identified environmental risks that predict subsequent psychological and medical problems. Based on these correlational findings, researchers have developed and tested complex developmental models and have examined biological moderating factors (e.g., gene–environment interactions). In this context, we stress the critical need for researchers to use family-based, quasi-experimental designs when trying to integrate genetic and social science research involving environmental variables because these designs rigorously examine causal inferences by testing competing hypotheses. We argue that sibling comparison, offspring of twins or siblings, in vitro fertilization designs, and other genetically informed approaches play a unique role in bridging gaps between basic biological and social science research. We use studies on maternal smoking during pregnancy to exemplify these principles. PMID:23927516

Physical methods for genetic transformation of fungi and yeast

NASA Astrophysics Data System (ADS)

Rivera, Ana Leonor; Magaña-Ortíz, Denis; Gómez-Lim, Miguel; Fernández, Francisco; Loske, Achim M.

2014-06-01

The production of transgenic fungi is a routine process. Currently, it is possible to insert genes from other fungi, viruses, bacteria and even animals, albeit with low efficiency, into the genomes of a number of fungal species. Genetic transformation requires the penetration of the transgene through the fungal cell wall, a process that can be facilitated by biological or physical methods. Novel methodologies for the efficient introduction of specific genes and stronger promoters are needed to increase production levels. A possible solution to this problem is the recently discovered shock-wave-mediated transformation. The objective of this article is to review the state of the art of the physical methods used for genetic fungi transformation and to describe some of the basic physics and molecular biology behind them.

Critical need for family-based, quasi-experimental designs in integrating genetic and social science research.

PubMed

D'Onofrio, Brian M; Lahey, Benjamin B; Turkheimer, Eric; Lichtenstein, Paul

2013-10-01

Researchers have identified environmental risks that predict subsequent psychological and medical problems. Based on these correlational findings, researchers have developed and tested complex developmental models and have examined biological moderating factors (e.g., gene-environment interactions). In this context, we stress the critical need for researchers to use family-based, quasi-experimental designs when trying to integrate genetic and social science research involving environmental variables because these designs rigorously examine causal inferences by testing competing hypotheses. We argue that sibling comparison, offspring of twins or siblings, in vitro fertilization designs, and other genetically informed approaches play a unique role in bridging gaps between basic biological and social science research. We use studies on maternal smoking during pregnancy to exemplify these principles.

Heritability of personality disorder traits: a twin study.

PubMed

Jang, K L; Livesley, W J; Vernon, P A; Jackson, D N

1996-12-01

Genetic and non-genetic influences on the hierarchy of traits that delineate personality disorder as measured by the Dimensional Assessment of Personality Problems (DAPP-DQ) scale were examined using data from a sample of 483 volunteer twin pairs (236 monozygotic pairs and 247 dizygotic pairs). The DAPP-DQ assesses four higher-order factors, 18 basic dimensions and 69 facet traits of personality disorder. The correlation coefficients for monozygotic and dizygotic twin pairs ranged from 0.26 to 0.56 and from 0.03 to 0.41, respectively. Broad heritability estimates ranged from 0 to 58% (median value 45%). Additive genetic effects and unique environmental effects emerged as the primary influences on these scales, with unique environmental influences accounting for the largest proportion of the variance for most traits at all levels of the hierarchy.

The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

PubMed Central

Guerra, Daniel J.

2011-01-01

Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD. PMID:22937247

Study of genetic direct search algorithms for function optimization

NASA Technical Reports Server (NTRS)

Zeigler, B. P.

1974-01-01

The results are presented of a study to determine the performance of genetic direct search algorithms in solving function optimization problems arising in the optimal and adaptive control areas. The findings indicate that: (1) genetic algorithms can outperform standard algorithms in multimodal and/or noisy optimization situations, but suffer from lack of gradient exploitation facilities when gradient information can be utilized to guide the search. (2) For large populations, or low dimensional function spaces, mutation is a sufficient operator. However for small populations or high dimensional functions, crossover applied in about equal frequency with mutation is an optimum combination. (3) Complexity, in terms of storage space and running time, is significantly increased when population size is increased or the inversion operator, or the second level adaptation routine is added to the basic structure.

Advanced genetic tools for plant biotechnology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, WS; Yuan, JS; Stewart, CN

2013-10-09

Basic research has provided a much better understanding of the genetic networks and regulatory hierarchies in plants. To meet the challenges of agriculture, we must be able to rapidly translate this knowledge into generating improved plants. Therefore, in this Review, we discuss advanced tools that are currently available for use in plant biotechnology to produce new products in plants and to generate plants with new functions. These tools include synthetic promoters, 'tunable' transcription factors, genome-editing tools and site-specific recombinases. We also review some tools with the potential to enable crop improvement, such as methods for the assembly and synthesis ofmore » large DNA molecules, plant transformation with linked multigenes and plant artificial chromosomes. These genetic technologies should be integrated to realize their potential for applications to pressing agricultural and environmental problems.« less

Advanced genetic tools for plant biotechnology.

PubMed

Liu, Wusheng; Yuan, Joshua S; Stewart, C Neal

2013-11-01

Basic research has provided a much better understanding of the genetic networks and regulatory hierarchies in plants. To meet the challenges of agriculture, we must be able to rapidly translate this knowledge into generating improved plants. Therefore, in this Review, we discuss advanced tools that are currently available for use in plant biotechnology to produce new products in plants and to generate plants with new functions. These tools include synthetic promoters, 'tunable' transcription factors, genome-editing tools and site-specific recombinases. We also review some tools with the potential to enable crop improvement, such as methods for the assembly and synthesis of large DNA molecules, plant transformation with linked multigenes and plant artificial chromosomes. These genetic technologies should be integrated to realize their potential for applications to pressing agricultural and environmental problems.

Primer in Genetics and Genomics, Article 5-Further Defining the Concepts of Genotype and Phenotype and Exploring Genotype-Phenotype Associations.

PubMed

Wright, Fay; Fessele, Kristen

2017-10-01

As nurses begin to incorporate genetic and genomic sciences into clinical practice, education, and research, it is essential that they have a working knowledge of the terms foundational to the science. The first article in this primer series provided brief definitions of the basic terms (e.g., genetics and genomics) and introduced the concept of phenotype during the discussion of Mendelian inheritance. These terms, however, are inconsistently used in publications and conversations, and the linkage between genotype and phenotype requires clarification. The goal of this fifth article in the series is to elucidate these terms, provide an overview of the research methods used to determine genotype-phenotype associations, and discuss their significance to nursing through examples from the current nursing literature.

Future translational applications from the contemporary genomics era: a scientific statement from the American Heart Association.

PubMed

Fox, Caroline S; Hall, Jennifer L; Arnett, Donna K; Ashley, Euan A; Delles, Christian; Engler, Mary B; Freeman, Mason W; Johnson, Julie A; Lanfear, David E; Liggett, Stephen B; Lusis, Aldons J; Loscalzo, Joseph; MacRae, Calum A; Musunuru, Kiran; Newby, L Kristin; O'Donnell, Christopher J; Rich, Stephen S; Terzic, Andre

2015-05-12

The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care. © 2015 American Heart Association, Inc.

Genetics-based methods for detection of Salmonella spp. in foods.

PubMed

Mozola, Mark A

2006-01-01

Genetic methods are now at the forefront of foodborne pathogen testing. The sensitivity, specificity, and inclusivity advantages offered by deoxyribonucleic acid (DNA) probe technology have driven an intense effort in methods development over the past 20 years. DNA probe-based methods for Salmonella spp. and other pathogens have progressed from time-consuming procedures involving the use of radioisotopes to simple, high throughput, automated assays. The analytical sensitivity of nucleic acid amplification technology has facilitated a reduction in analysis time by allowing enriched samples to be tested for previously undetectable quantities of analyte. This article will trace the evolution of the development of genetic methods for detection of Salmonella in foods, review the basic assay formats and their advantages and limitations, and discuss method performance characteristics and considerations for selection of methods.

Synthesizing genetic sequential logic circuit with clock pulse generator

PubMed Central

2014-01-01

Background Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. Results This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. Conclusions A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal. PMID:24884665

Modeling impacts of CO2, ozone, and climate change on tree growth

Treesearch

George E. Host; Gary W. Theseira; J. G. Isebrands

1996-01-01

Understanding the influence of ozone, CO2, and changing climatic regimes on basic plant physiological processes is essential for predicting the response of forest ecosystems. To understand the relationships among these interacting factors, in the face of genetic and other environmental variability, requires a means of synthesis. Physiological...

Who Do I Look Like? Diversity in Self, Family, and Others

ERIC Educational Resources Information Center

Mensah, Felicia Moore

2010-01-01

In this introductory, hands-on, multicultural genetics lesson for elementary students, the author describes an activity used to engage learners in understanding diversity in self, family, and others. Students make connections between traits within their family and learn a few basic concepts about inheritance. At the end of the lesson, the author…

Students' Bibliographic Research: Competition Enhances Results.

ERIC Educational Resources Information Center

Engel, Nora; And Others

1996-01-01

Describes an approach to a course about the basics of genetics and molecular biology that utilizes a contest that involves students in accessing information about a topic such as sex determination, neural development, and gene therapy. The general objective of the approach is to inspire students to become familiar with the scientific literature.…

From Mendel to the Human Genome Project: The Implications for Nurse Education.

ERIC Educational Resources Information Center

Burton, Hilary; Stewart, Alison

2003-01-01

The Human Genome Project is brining new opportunities to predict and prevent diseases. Although pediatric nurses are the closest to these developments, most nurses will encounter genetic aspects of practice and must understand the basic science and its ethical, legal, and social dimensions. (Includes commentary by Peter Birchenall.) (SK)

Enhancing Subjective Well-Being in Individuals with Asthma

ERIC Educational Resources Information Center

Bray, Melissa A.; Kehle, Thomas J.; Peck, Heather L.; Theodore, Lea A.; Zhou, Zheng

2004-01-01

Asthma, a chronic respiratory disease, is caused by a complex interaction between genetic and environmental variables. The intent of this article is to propose a theory that provides an explanation for the reduction of emotionally triggered asthma through treatments derived from positive psychology. The basic tenet of the theory is that physical…

New carrot and garlic germplasm to advance breeding and understand crop origins

USDA-ARS?s Scientific Manuscript database

The genetic variation provided by diverse plant germplasm is the basic building material used for crop improvement that shapes the crops we grow today. Wild carrot from the U.S. provided the cytoplasm used to develop a reliable system to produce hybrid carrots that account for most of the commercial...

Introduction to the Special Section on Epigenetics

ERIC Educational Resources Information Center

Lester, Barry M.; Conradt, Elisabeth; Marsit, Carmen

2016-01-01

Epigenetics provides the opportunity to revolutionize our understanding of the role of genetics and the environment in explaining human behavior, although the use of epigenetics to study human behavior is just beginning. In this introduction, the authors present the basics of epigenetics in a way that is designed to make this exciting field…

A Rapid PCR-RFLP Method for Monitoring Genetic Variation among Commercial Mushroom Species

ERIC Educational Resources Information Center

Martin, Presley; Muruke, Masoud; Hosea, Kenneth; Kivaisi, Amelia; Zerwas, Nick; Bauerle, Cynthia

2004-01-01

We report the development of a simplified procedure for restriction fragment length polymorphism (RFLP) analysis of mushrooms. We have adapted standard molecular techniques to be amenable to an undergraduate laboratory setting in order to allow students to explore basic questions about fungal diversity and relatedness among mushroom species. The…

Beyond Busing: A Societal and Genetic View.

ERIC Educational Resources Information Center

Carrison, Muriel Paskin

In this paper the author takes the position that integrated schools are basic to a genuinely integrated society. Similarly, only through equal education can we offer equal opportunity to every citizen. Segregated schools, the author states, are a result of poverty and government sanctioned segregation in other areas. The most obvious of these…

The Formation Experiment in the Age of Hypermedia and Distance Learning

ERIC Educational Resources Information Center

Giest, Hartmut

2004-01-01

Searching for an adequate method to investigate human development (especially the development of theoretical thinking) Vygotsky and his collaborators developed the causal genetic method. The basic idea of this method consists in the investigation of psychic functions and structures by their formation under controlled conditions (for instance via a…

How Do Siamese Cats Get Their Color?

ERIC Educational Resources Information Center

Todd, Amber; Kenyon, Lisa

2016-01-01

When asked about protein, students often mention meat, protein bars, and protein's role in building muscles. Many students are not aware of the most basic function of protein: linking genes and traits. Because of its importance in molecular genetics, protein function is included in the life sciences section of the "Next Generation Science…

Food Allergy - Basic Mechanisms and Applications to Identifying Risks Associated with Plant Incorporated Pesticides and Other Genetically Modified Crops

EPA Science Inventory

Food allergy is a relatively new concern for toxicologists as a result of the incorporation of novel proteins into food crops in order to promote resistance to pests and other stresses, improve nutrition, or otherwise modify the phenotype. Food allergy can manifest as inflammatio...

Annual Review of Psychology. Volume 22, 1971.

ERIC Educational Resources Information Center

Mussen, Paul H., Ed.; Rosenzweig, Mark R., Ed.

The Annual Review of Psychology is compiled to provide authoritative evaluation of progress in both the traditional and the new areas of psychology. The 1971 edition includes the following topics and authors: Basic Drives, by Frank W. Finger and Douglas G. Mook; Behavioral Genetics, by Gardner Lindzey and others; Audition, by David H. Raab;…

The War with Words: Structure and Transcendence. Approaches to Semiotics Series No. 12.

ERIC Educational Resources Information Center

Shands, Harley C.

Semiotic research increasingly reveals the basic importance of structure at all levels of genetic, linguistic, and social process. The paradox that structure not only liberates but also imprisons has been familiar to members of many different cultures, and the search for personal release in transcendent states of feeling contrapuntally illuminates…

Streptococcus mutans: a new Gram-positive paradigm?

PubMed Central

Quivey, Robert G.; Koo, Hyun; Abranches, Jacqueline

2013-01-01

Despite the enormous contributions of the bacterial paradigms Escherichia coli and Bacillus subtilis to basic and applied research, it is well known that no single organism can be a perfect representative of all other species. However, given that some bacteria are difficult, or virtually impossible, to cultivate in the laboratory, that some are recalcitrant to genetic and molecular manipulation, and that others can be extremely dangerous to manipulate, the use of model organisms will continue to play an important role in the development of basic research. In particular, model organisms are very useful for providing a better understanding of the biology of closely related species. Here, we discuss how the lifestyle, the availability of suitable in vitro and in vivo systems, and a thorough understanding of the genetics, biochemistry and physiology of the dental pathogen Streptococcus mutans have greatly advanced our understanding of important areas in the field of bacteriology such as interspecies biofilms, competence development and stress responses. In this article, we provide an argument that places S. mutans, an organism that evolved in close association with the human host, as a novel Gram-positive model organism. PMID:23393147

From chemical metabolism to life: the origin of the genetic coding process

PubMed Central

2017-01-01

Looking for origins is so much rooted in ideology that most studies reflect opinions that fail to explore the first realistic scenarios. To be sure, trying to understand the origins of life should be based on what we know of current chemistry in the solar system and beyond. There, amino acids and very small compounds such as carbon dioxide, dihydrogen or dinitrogen and their immediate derivatives are ubiquitous. Surface-based chemical metabolism using these basic chemicals is the most likely beginning in which amino acids, coenzymes and phosphate-based small carbon molecules were built up. Nucleotides, and of course RNAs, must have come to being much later. As a consequence, the key question to account for life is to understand how chemical metabolism that began with amino acids progressively shaped into a coding process involving RNAs. Here I explore the role of building up complementarity rules as the first information-based process that allowed for the genetic code to emerge, after RNAs were substituted to surfaces to carry over the basic metabolic pathways that drive the pursuit of life. PMID:28684991

Carbohydrate and energy-yielding metabolism in non-conventional yeasts.

PubMed

Flores, C L; Rodríguez, C; Petit, T; Gancedo, C

2000-10-01

Sugars are excellent carbon sources for all yeasts. Since a vast amount of information is available on the components of the pathways of sugar utilization in Saccharomyces cerevisiae it has been tacitly assumed that other yeasts use sugars in the same way. However, although the pathways of sugar utilization follow the same theme in all yeasts, important biochemical and genetic variations on it exist. Basically, in most non-conventional yeasts, in contrast to S. cerevisiae, respiration in the presence of oxygen is prominent for the use of sugars. This review provides comparative information on the different steps of the fundamental pathways of sugar utilization in non-conventional yeasts: glycolysis, fermentation, tricarboxylic acid cycle, pentose phosphate pathway and respiration. We consider also gluconeogenesis and, briefly, catabolite repression. We have centered our attention in the genera Kluyveromyces, Candida, Pichia, Yarrowia and Schizosaccharomyces, although occasional reference to other genera is made. The review shows that basic knowledge is missing on many components of these pathways and also that studies on regulation of critical steps are scarce. Information on these points would be important to generate genetically engineered yeast strains for certain industrial uses.

Animal models of neoplastic development.

PubMed

Pitot, H C

2001-01-01

The basic animal model for neoplastic development used by regulatory agencies is the two-year chronic bioassay developed more than 30 years ago and based on the presumed mechanism of action of a few potential chemical carcinogens. Since that time, a variety of other model carcinogenic systems have been developed, usually involving shorter duration, single organ endpoints, multistage models, and those in genetically-engineered mice. The chronic bioassay is still the "gold standard" of regulatory agencies despite a number of deficiencies, while in this country the use of shorter term assays based on single organ endpoints has not been popular. The multistage model of carcinogenesis in mouse epidermis actually preceded the development of the chronic two-year bioassay, but it was not until multistage models in other organ systems were developed that the usefulness of such systems became apparent. Recently, several genetically-engineered mouse lines involving mutations in proto-oncogenes and tumour suppressor genes have been proposed as additional model systems for use in regulatory decisions. It is likely that a combination of several of these model systems may be most useful in both practical and basic applications of cancer prevention and therapy.

Genetic engineering of somatic cells to study and improve cardiac function.

PubMed

Kirkton, Robert D; Bursac, Nenad

2012-11-01

To demonstrate the utility of genetically engineered excitable cells for studies of basic electrophysiology and cardiac cell therapy. 'Zig-zag' networks of neonatal rat ventricular myocytes (NRVMs) were micropatterned onto thin elastomeric films to mimic the slow action potential (AP) conduction found in fibrotic myocardium. Addition of genetically engineered excitable human embryonic kidney cells (HEK-293 cells) ('Ex-293' cells stably expressing Kir2.1, Na(v)1.5, and Cx43 channels) increased both cardiac conduction velocity by 370% and twitch force amplitude by 64%. Furthermore, we stably expressed mutant Na(v)1.5 [A1924T (fast sodium channel mutant (substitution of alanine by threonine at amino acid 1924)] channels with hyperpolarized steady-state activation and showed that, despite a 71.6% reduction in peak I(Na), these cells propagated APs at the same velocity as the wild-type Na(v)1.5-expressing Ex-293 cells. Stable expression of Ca(v)3.3 (T-type voltage-gated calcium) channels in Ex-293 cells (to generate an 'ExCa-293' line) significantly increased their AP duration and reduced repolarization gradients in cocultures of these cells and NRVMs. Additional expression of an optogenetic construct [ChIEF (light-gated Channelrhodopsin mutant)]enabled light-based control of AP firing in ExCa-293 cells. We show that, despite being non-contractile, genetically engineered excitable cells can significantly improve both electrical and mechanical function of engineered cardiac tissues in vitro. We further demonstrate the utility of engineered cells for tissue-level studies of basic electrophysiology and cardiac channelopathies. In the future, this novel platform could be utilized in the high-throughput design of new genetically encoded indicators of cell electrical function, validation, and improvement of computer models of AP conduction, and development of novel engineered somatic cell therapies for the treatment of cardiac infarction and arrhythmias.

Strong genetic overlap between executive functions and intelligence.

PubMed

Engelhardt, Laura E; Mann, Frank D; Briley, Daniel A; Church, Jessica A; Harden, K Paige; Tucker-Drob, Elliot M

2016-09-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Genetic and Epigenetic Variations Induced by Wheat-Rye 2R and 5R Monosomic Addition Lines

PubMed Central

Fu, Shulan; Sun, Chuanfei; Yang, Manyu; Fei, Yunyan; Tan, Feiqun; Yan, Benju; Ren, Zhenglong; Tang, Zongxiang

2013-01-01

Background Monosomic alien addition lines (MAALs) can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. Methodology/Principal Findings In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. Conclusions/Significance The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat. PMID:23342073

Genetic and epigenetic variations induced by wheat-rye 2R and 5R monosomic addition lines.

PubMed

Fu, Shulan; Sun, Chuanfei; Yang, Manyu; Fei, Yunyan; Tan, Feiqun; Yan, Benju; Ren, Zhenglong; Tang, Zongxiang

2013-01-01

Monosomic alien addition lines (MAALs) can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat.

CTGA: the database for genetic disorders in Arab populations.

PubMed

Tadmouri, Ghazi O; Al Ali, Mahmoud Taleb; Al-Haj Ali, Sarah; Al Khaja, Najib

2006-01-01

The Arabs comprise a genetically heterogeneous group that resulted from the admixture of different populations throughout history. They share many common characteristics responsible for a considerable proportion of perinatal and neonatal mortalities. To this end, the Centre for Arab Genomic Studies (CAGS) launched a pilot project to construct the 'Catalogue of Transmission Genetics in Arabs' (CTGA) database for genetic disorders in Arabs. Information in CTGA is drawn from published research and mined hospital records. The database offers web-based basic and advanced search approaches. In either case, the final search result is a detailed HTML record that includes text-, URL- and graphic-based fields. At present, CTGA hosts entries for 692 phenotypes and 235 related genes described in Arab individuals. Of these, 213 phenotypic descriptions and 22 related genes were observed in the Arab population of the United Arab Emirates (UAE). These results emphasize the role of CTGA as an essential tool to promote scientific research on genetic disorders in the region. The priority of CTGA is to provide timely information on the occurrence of genetic disorders in Arab individuals. It is anticipated that data from Arab countries other than the UAE will be exhaustively searched and incorporated in CTGA (http://www.cags.org.ae).

The emergence of human-evolutionary medical genomics

PubMed Central

Crespi, Bernard J

2011-01-01

In this review, I describe how evolutionary genomics is uniquely suited to spearhead advances in understanding human disease risk, owing to the privileged position of genes as fundamental causes of phenotypic variation, and the ability of population genetic and phylogenetic methods to robustly infer processes of natural selection, drift, and mutation from genetic variation at the levels of family, population, species, and clade. I first provide an overview of models for the origins and maintenance of genetically based disease risk in humans. I then discuss how analyses of genetic disease risk can be dovetailed with studies of positive and balancing selection, to evaluate the degree to which the ‘genes that make us human’ also represent the genes that mediate risk of polygenic disease. Finally, I present four basic principles for the nascent field of human evolutionary medical genomics, each of which represents a process that is nonintuitive from a proximate perspective. Joint consideration of these principles compels novel forms of interdisciplinary analyses, most notably studies that (i) analyze tradeoffs at the level of molecular genetics, and (ii) identify genetic variants that are derived in the human lineage or in specific populations, and then compare individuals with derived versus ancestral alleles. PMID:25567974

The Genetics of Infertility: Current Status of the Field

PubMed Central

Zorrilla, Michelle; Yatsenko, Alexander N

2013-01-01

Infertility is a relatively common health condition, affecting nearly 7% of all couples. Clinically, it is a highly heterogeneous pathology with a complex etiology that includes environmental and genetic factors. It has been estimated that nearly 50% of infertility cases are due to genetic defects. Hundreds of studies with animal knockout models convincingly showed infertility to be caused by gene defects, single or multiple. However, despite enormous efforts, progress in translating basic research findings into clinical studies has been challenging. The genetic causes remain unexplained for the vast majority of male or female infertility patients. A particular difficulty is the huge number of candidate genes to be studied; there are more than 2,300 genes expressed in the testis alone, and hundreds of those genes influence reproductive function in humans and could contribute to male infertility. At present, there are only a handful of genes or genetic defects that have been shown to cause, or to be strongly associated with, primary infertility. Yet, with completion of the human genome and progress in personalized medicine, the situation is rapidly changing. Indeed, there are 10-15 new gene tests, on average, being added to the clinical genetic testing list annually. PMID:24416713

CTGA: the database for genetic disorders in Arab populations

PubMed Central

Tadmouri, Ghazi O.; Ali, Mahmoud Taleb Al; Ali, Sarah Al-Haj; Khaja, Najib Al

2006-01-01

The Arabs comprise a genetically heterogeneous group that resulted from the admixture of different populations throughout history. They share many common characteristics responsible for a considerable proportion of perinatal and neonatal mortalities. To this end, the Centre for Arab Genomic Studies (CAGS) launched a pilot project to construct the ‘Catalogue of Transmission Genetics in Arabs’ (CTGA) database for genetic disorders in Arabs. Information in CTGA is drawn from published research and mined hospital records. The database offers web-based basic and advanced search approaches. In either case, the final search result is a detailed HTML record that includes text-, URL- and graphic-based fields. At present, CTGA hosts entries for 692 phenotypes and 235 related genes described in Arab individuals. Of these, 213 phenotypic descriptions and 22 related genes were observed in the Arab population of the United Arab Emirates (UAE). These results emphasize the role of CTGA as an essential tool to promote scientific research on genetic disorders in the region. The priority of CTGA is to provide timely information on the occurrence of genetic disorders in Arab individuals. It is anticipated that data from Arab countries other than the UAE will be exhaustively searched and incorporated in CTGA (). PMID:16381941

Initiating a Human Variome Project Country Node.

PubMed

AlAama, Jumana; Smith, Timothy D; Lo, Alan; Howard, Heather; Kline, Alexandria A; Lange, Matthew; Kaput, Jim; Cotton, Richard G H

2011-05-01

Genetic diseases are a pressing global health problem that requires comprehensive access to basic clinical and genetic data to counter. The creation of regional and international databases that can be easily accessed by clinicians and diagnostic labs will greatly improve our ability to accurately diagnose and treat patients with genetic disorders. The Human Variome Project is currently working in conjunction with human genetics societies to achieve this by establishing systems to collect every mutation reported by a diagnostic laboratory, clinic, or research laboratory in a country and store these within a national repository, or HVP Country Node. Nodes have already been initiated in Australia, Belgium, China, Egypt, Malaysia, and Kuwait. Each is examining how to systematically collect and share genetic, clinical, and biochemical information in a country-specific manner that is sensitive to local ethical and cultural issues. This article gathers cases of genetic data collection within countries and takes recommendations from the global community to develop a procedure for countries wishing to establish their own collection system as part of the Human Variome Project. We hope this may lead to standard practices to facilitate global collection of data and allow efficient use in clinical practice, research and therapy. © 2011 Wiley-Liss, Inc.

[Impacts of genetically modified soybean leaf residues on Folsomia candida.

PubMed

Zhou, Lin; Wang, Bai Feng; Liu, Xin Ying; Jiang, Ying; Wang, Da Ming; Feng, Shu Dan; Song, Xin Yuan

2016-09-01

When the genetically modified soybean is planted in the field, the expression product of exogenous gene could be exposed in the soil ecosystem and bring potential risk to the soil fauna, with the form of leaves and other debris. A few of genetically modified soybeans developed by China independently were used in our study as materials. They were Phytophthora-resistant soybean harboring hrpZm gene (B4J8049), leaf-feeding insect-resistant soybean harboring Cry1C gene (A2A8001) and Leguminivora glycinivorella-resistant soybean harboring Cry1Iem gene (C802). By feeding Folsomia candida with the three genetically modified soybeans for continuous 60 days, the surviving rate, reproductive rate and changes on the body length of F. candida were studied. The results showed that all the three genetically modified soybeans of B4J8049, A2A8001 and C802 had no significant adverse effects on the growth of F. candida, as an environmental indicator organism. It was initially inferred that they were environmentally safe under short-term exposure, which provided basic data of ecological safety for their wide cultivation.

Finding the Genomic Basis of Local Adaptation: Pitfalls, Practical Solutions, and Future Directions.

PubMed

Hoban, Sean; Kelley, Joanna L; Lotterhos, Katie E; Antolin, Michael F; Bradburd, Gideon; Lowry, David B; Poss, Mary L; Reed, Laura K; Storfer, Andrew; Whitlock, Michael C

2016-10-01

Uncovering the genetic and evolutionary basis of local adaptation is a major focus of evolutionary biology. The recent development of cost-effective methods for obtaining high-quality genome-scale data makes it possible to identify some of the loci responsible for adaptive differences among populations. Two basic approaches for identifying putatively locally adaptive loci have been developed and are broadly used: one that identifies loci with unusually high genetic differentiation among populations (differentiation outlier methods) and one that searches for correlations between local population allele frequencies and local environments (genetic-environment association methods). Here, we review the promises and challenges of these genome scan methods, including correcting for the confounding influence of a species' demographic history, biases caused by missing aspects of the genome, matching scales of environmental data with population structure, and other statistical considerations. In each case, we make suggestions for best practices for maximizing the accuracy and efficiency of genome scans to detect the underlying genetic basis of local adaptation. With attention to their current limitations, genome scan methods can be an important tool in finding the genetic basis of adaptive evolutionary change.

Studies on nonsense mediated decay reveal novel therapeutic options for genetic diseases.

PubMed

Bashyam, Murali D

2009-01-01

Scientific breakthroughs have often led to commercially viable patents mainly in the field of engineering. Commercialization in the field of medicine has been restricted mostly to machinery and engineering on the one hand and therapeutic drugs for common chronic ailments such as cough, cold, headache, etc, on the other. Sequencing of the human genome has attracted the attention of pharmaceutical companies and now biotechnology has become a goldmine for commercialization of products and processes. Recent advances in our understanding of basic biological processes have resulted in the opening of new avenues for treatment of human genetic diseases, especially single gene disorders. A significant proportion of human genetic disorders have been shown to be caused due to degradation of transcripts for specific genes through a process called nonsense mediated decay (NMD). The modulation of NMD provides a viable therapeutic option for treatment of several genetic disorders and therefore has been a good prospect for patenting and commercialization. In this review the molecular basis for NMD and attempts to treat genetic diseases which result from NMD are discussed.

Chemical genetics - a versatile method to combine science and higher level teaching in molecular genetics.

PubMed

Sandrock, Björn

2012-10-09

Phosphorylation is a key event in many cellular processes like cell cycle, transformation of environmental signals to transcriptional activation or polar growth. The chemical genetics approach can be used to analyse the effect of highly specific inhibition in vivo and is a promising method to screen for kinase targets. We have used this approach to study the role of the germinal centre kinase Don3 during the cell division in the phytopathogenic fungus Ustilago maydis. Due to the easy determination of the don3 phenotype we have chosen this approach for a genetic course for M.Sc. students and for IMPRS (International Max-Planck research school) students. According to the principle of "problem-based learning" the aim of this two-week course is to transfer knowledge about the broad spectrum of kinases to the students and that the students acquire the ability to design their own analog-sensitive kinase of interest. In addition to these training goals, we benefit from these annual courses the synthesis of basic constructs for genetic modification of several kinases in our model system U. maydis.

Impact of US Brown Swiss genetics on milk quality from low-input herds in Switzerland: Interactions with season.

PubMed

Stergiadis, Sokratis; Bieber, Anna; Chatzidimitriou, Eleni; Franceschin, Enrica; Isensee, Anne; Rempelos, Leonidas; Baranski, Marcin; Maurer, Veronika; Cozzi, Giulio; Bapst, Beat; Butler, Gillian; Leifert, Carlo

2018-06-15

This study investigated the effect of, and interactions between, US Brown Swiss (BS) genetics and season on milk yield, basic composition and fatty acid profiles, from cows on low-input farms in Switzerland. Milk samples (n = 1,976) were collected from 1,220 crossbreed cows with differing proportions of BS, Braunvieh and Original Braunvieh genetics on 40 farms during winter-housing and summer-grazing. Cows with more BS genetics produced more milk in winter but not in summer, possibly because of underfeeding potentially high-yielding cows on low-input pasture-based diets. Cows with more Original Braunvieh genetics produced milk with more (i) nutritionally desirable eicosapentaenoic and docosapentaenoic acids, throughout the year, and (ii) vaccenic and α-linolenic acids, total omega-3 fatty acid concentrations and a higher omega-3/omega-6 ratio only during summer-grazing. This suggests that overall milk quality could be improved by re-focussing breeding strategies on cows' ability to respond to local dietary environments and seasonal dietary changes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evolutionary developmental genetics of fruit morphological variation within the Solanaceae

PubMed Central

Wang, Li; Li, Jing; Zhao, Jing; He, Chaoying

2015-01-01

Morphological variations of fruits such as shape and size, and color are a result of adaptive evolution. The evolution of morphological novelties is particularly intriguing. An understanding of these evolutionary processes calls for the elucidation of the developmental and genetic mechanisms that result in particular fruit morphological characteristics, which determine seed dispersal. The genetic and developmental basis for fruit morphological variation was established at a microevolutionary time scale. Here, we summarize the progress on the evolutionary developmental genetics of fruit size, shape and color in the Solanaceae. Studies suggest that the recruitment of a pre-existing gene and subsequent modification of its interaction and regulatory networks are frequently involved in the evolution of morphological diversity. The basic mechanisms underlying changes in plant morphology are alterations in gene expression and/or gene function. We also deliberate on the future direction in evolutionary developmental genetics of fruit morphological variation such as fruit type. These studies will provide insights into plant developmental processes and will help to improve the productivity and fruit quality of crops. PMID:25918515

Human genetics for non-scientists: Practical workshops for policy makers and opinion leaders

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-12-31

These workshops form part of a series of workshops that the Banbury and the DNA Learning Centers of Cold Spring Harbor Laboratory have held for a number of years, introducing genetics, and the ways in which scientific research is done, to non-scientists. The purpose of the workshops as stated in the grant application was: {open_quotes}Our objective is to foster a better understanding of the societal impact of human genome research by providing basic information on genetics to non-scientists whose professions or special interests interface with genetic technology.... Participants will be chosen for their interest in human genetics and for theirmore » roles as opinion leaders in their own communities. Primary care physicians are of particular interest to us for this series of workshops.{close_quotes} Two workshops were held under this grant. The first was held in 21-24 April, 1994 and attended by 20 participants, and the second was held 16-19 November, 1995, and attended by 16 participants. In each case, there was a combination of concept lectures on the foundations of human molecular genetics; lectures by invited specialists; and laboratory experiments to introduce non-scientists to the techniques used in molecular genetics.« less

[Sporulation or competence development? A genetic regulatory network model of cell-fate determination in Bacillus subtilis].

PubMed

Lu, Zhenghui; Zhou, Yuling; Zhang, Xiaozhou; Zhang, Guimin

2015-11-01

Bacillus subtilis is a generally recognized as safe (GRAS) strain that has been widely used in industries including fodder, food, and biological control. In addition, B. subtilis expression system also plays a significant role in the production of industrial enzymes. However, its application is limited by its low sporulation frequency and transformation efficiency. Immense studies have been done on interpreting the molecular mechanisms of sporulation and competence development, whereas only few of them were focused on improving sporulation frequency and transformation efficiency of B. subtilis by genetic modification. The main challenge is that sporulation and competence development, as the two major developmental events in the stationary phase of B. subtilis, are regulated by the complicated intracellular genetic regulatory systems. In addition, mutual regulatory mechanisms also exist in these two developmental events. With the development of genetic and metabolic engineering, constructing genetic regulatory networks is currently one of the most attractive research fields, together with the genetic information of cell growth, metabolism, and development, to guide the industrial application. In this review, the mechanisms of sporulation and competence development of B. subtilis, their interactions, and the genetic regulation of cell growth were interpreted. In addition, the roles of these regulatory networks in guiding basic and applied research of B. subtilis and its related species were discussed.

Computational power and generative capacity of genetic systems.

PubMed

Igamberdiev, Abir U; Shklovskiy-Kordi, Nikita E

2016-01-01

Semiotic characteristics of genetic sequences are based on the general principles of linguistics formulated by Ferdinand de Saussure, such as the arbitrariness of sign and the linear nature of the signifier. Besides these semiotic features that are attributable to the basic structure of the genetic code, the principle of generativity of genetic language is important for understanding biological transformations. The problem of generativity in genetic systems arises to a possibility of different interpretations of genetic texts, and corresponds to what Alexander von Humboldt called "the infinite use of finite means". These interpretations appear in the individual development as the spatiotemporal sequences of realizations of different textual meanings, as well as the emergence of hyper-textual statements about the text itself, which underlies the process of biological evolution. These interpretations are accomplished at the level of the readout of genetic texts by the structures defined by Efim Liberman as "the molecular computer of cell", which includes DNA, RNA and the corresponding enzymes operating with molecular addresses. The molecular computer performs physically manifested mathematical operations and possesses both reading and writing capacities. Generativity paradoxically resides in the biological computational system as a possibility to incorporate meta-statements about the system, and thus establishes the internal capacity for its evolution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Structure-function analysis of genetically defined neuronal populations.

PubMed

Groh, Alexander; Krieger, Patrik

2013-10-01

Morphological and functional classification of individual neurons is a crucial aspect of the characterization of neuronal networks. Systematic structural and functional analysis of individual neurons is now possible using transgenic mice with genetically defined neurons that can be visualized in vivo or in brain slice preparations. Genetically defined neurons are useful for studying a particular class of neurons and also for more comprehensive studies of the neuronal content of a network. Specific subsets of neurons can be identified by fluorescence imaging of enhanced green fluorescent protein (eGFP) or another fluorophore expressed under the control of a cell-type-specific promoter. The advantages of such genetically defined neurons are not only their homogeneity and suitability for systematic descriptions of networks, but also their tremendous potential for cell-type-specific manipulation of neuronal networks in vivo. This article describes a selection of procedures for visualizing and studying the anatomy and physiology of genetically defined neurons in transgenic mice. We provide information about basic equipment, reagents, procedures, and analytical approaches for obtaining three-dimensional (3D) cell morphologies and determining the axonal input and output of genetically defined neurons. We exemplify with genetically labeled cortical neurons, but the procedures are applicable to other brain regions with little or no alterations.

Studying circadian rhythm and sleep using genetic screens in Drosophila.

PubMed

Axelrod, Sofia; Saez, Lino; Young, Michael W

2015-01-01

The power of Drosophila melanogaster as a model organism lies in its ability to be used for large-scale genetic screens with the capacity to uncover the genetic basis of biological processes. In particular, genetic screens for circadian behavior, which have been performed since 1971, allowed researchers to make groundbreaking discoveries on multiple levels: they discovered that there is a genetic basis for circadian behavior, they identified the so-called core clock genes that govern this process, and they started to paint a detailed picture of the molecular functions of these clock genes and their encoded proteins. Since the discovery that fruit flies sleep in 2000, researchers have successfully been using genetic screening to elucidate the many questions surrounding this basic animal behavior. In this chapter, we briefly recall the history of circadian rhythm and sleep screens and then move on to describe techniques currently employed for mutagenesis and genetic screening in the field. The emphasis lies on comparing the newer approaches of transgenic RNA interference (RNAi) to classical forms of mutagenesis, in particular in their application to circadian behavior and sleep. We discuss the different screening approaches in light of the literature and published and unpublished sleep and rhythm screens utilizing ethyl methanesulfonate mutagenesis and transgenic RNAi from our lab. © 2015 Elsevier Inc. All rights reserved.

Measuring genetic knowledge: a brief survey instrument for adolescents and adults.

PubMed

Fitzgerald-Butt, S M; Bodine, A; Fry, K M; Ash, J; Zaidi, A N; Garg, V; Gerhardt, C A; McBride, K L

2016-02-01

Basic knowledge of genetics is essential for understanding genetic testing and counseling. The lack of a written, English language, validated, published measure has limited our ability to evaluate genetic knowledge of patients and families. Here, we begin the psychometric analysis of a true/false genetic knowledge measure. The 18-item measure was completed by parents of children with congenital heart defects (CHD) (n = 465) and adolescents and young adults with CHD (age: 15-25, n = 196) with a mean total correct score of 12.6 [standard deviation (SD) = 3.5, range: 0-18]. Utilizing exploratory factor analysis, we determined that one to three correlated factors, or abilities, were captured by our measure. Through confirmatory factor analysis, we determined that the two factor model was the best fit. Although it was necessary to remove two items, the remaining items exhibited adequate psychometric properties in a multidimensional item response theory analysis. Scores for each factor were computed, and a sum-score conversion table was derived. We conclude that this genetic knowledge measure discriminates best at low knowledge levels and is therefore well suited to determine a minimum adequate amount of genetic knowledge. However, further reliability testing and validation in diverse research and clinical settings is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ceratopteris richardii: a productive model for revealing secrets of signaling and development

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Roux, S. J.

2000-01-01

Ceratopteris richardii is an aquatic fern grown in tropical and subtropical regions of the world. It is proven to be a productive model system for studies in the genetics, biochemistry, and cell biology of basic biologic processes that occur in early gametophytic development. It provides several advantages to biologists, especially those interested in gravitational biology, polarity development, and in the genetics of sexual development. It is easy to culture, has a relatively short life cycle, and offers an array of attractive features that facilitate genetic studies. The germination and early development of large populations of genetically identical spores are easy to synchronize, and both the direction of polarity development and cell-level gravity responses can be measured and readily manipulated within the first 24 h of spore development. Although there is no reliable transformation system available yet in Ceratopteris, recent studies suggest that the technique of RNA interference can be used to block translation of specific genes in a related fern, Marsilea, and current studies will soon reveal the applicability of this approach, as well as of other transformation approaches, in Ceratopteris. A recently completed expressed sequence tag (EST) sequencing project makes available the partial sequence of more than 2000 cDNAs, representing a significant percentage of the genes being expressed during the first 24 h of spore germination, when many developmentally interesting processes are occurring. A microarray of these ESTs is being constructed, so especially for those scientists interested in basic cellular phenomena that occur early in spore germination, the availability of the ESTs and of the microarray will make Ceratopteris an even more attractive model system.

Ceratopteris richardii: a productive model for revealing secrets of signaling and development.

PubMed

Chatterjee, A; Roux, S J

2000-09-01

Ceratopteris richardii is an aquatic fern grown in tropical and subtropical regions of the world. It is proven to be a productive model system for studies in the genetics, biochemistry, and cell biology of basic biologic processes that occur in early gametophytic development. It provides several advantages to biologists, especially those interested in gravitational biology, polarity development, and in the genetics of sexual development. It is easy to culture, has a relatively short life cycle, and offers an array of attractive features that facilitate genetic studies. The germination and early development of large populations of genetically identical spores are easy to synchronize, and both the direction of polarity development and cell-level gravity responses can be measured and readily manipulated within the first 24 h of spore development. Although there is no reliable transformation system available yet in Ceratopteris, recent studies suggest that the technique of RNA interference can be used to block translation of specific genes in a related fern, Marsilea, and current studies will soon reveal the applicability of this approach, as well as of other transformation approaches, in Ceratopteris. A recently completed expressed sequence tag (EST) sequencing project makes available the partial sequence of more than 2000 cDNAs, representing a significant percentage of the genes being expressed during the first 24 h of spore germination, when many developmentally interesting processes are occurring. A microarray of these ESTs is being constructed, so especially for those scientists interested in basic cellular phenomena that occur early in spore germination, the availability of the ESTs and of the microarray will make Ceratopteris an even more attractive model system.

Landscape genetics of high mountain frog metapopulations

USGS Publications Warehouse

Murphy, M.A.; Dezzani, R.; Pilliod, D.S.; Storfer, A.

2010-01-01

Explaining functional connectivity among occupied habitats is crucial for understanding metapopulation dynamics and species ecology. Landscape genetics has primarily focused on elucidating how ecological features between observations influence gene flow. Functional connectivity, however, may be the result of both these between-site (landscape resistance) landscape characteristics and at-site (patch quality) landscape processes that can be captured using network based models. We test hypotheses of functional connectivity that include both between-site and at-site landscape processes in metapopulations of Columbia spotted frogs (Rana luteiventris) by employing a novel justification of gravity models for landscape genetics (eight microsatellite loci, 37 sites, n = 441). Primarily used in transportation and economic geography, gravity models are a unique approach as flow (e.g. gene flow) is explained as a function of three basic components: distance between sites, production/attraction (e.g. at-site landscape process) and resistance (e.g. between-site landscape process). The study system contains a network of nutrient poor high mountain lakes where we hypothesized a short growing season and complex topography between sites limit R. luteiventris gene flow. In addition, we hypothesized production of offspring is limited by breeding site characteristics such as the introduction of predatory fish and inherent site productivity. We found that R. luteiventris connectivity was negatively correlated with distance between sites, presence of predatory fish (at-site) and topographic complexity (between-site). Conversely, site productivity (as measured by heat load index, at-site) and growing season (as measured by frost-free period between-sites) were positively correlated with gene flow. The negative effect of predation and positive effect of site productivity, in concert with bottleneck tests, support the presence of source-sink dynamics. In conclusion, gravity models provide a powerful new modelling approach for examining a wide range of both basic and applied questions in landscape genetics.

Zika Virus: The Agent and Its Biology, With Relevance to Pathology.

PubMed

Medin, Carey L; Rothman, Alan L

2017-01-01

Once obscure, Zika virus (ZIKV) has attracted significant medical and scientific attention in the past year because of large outbreaks associated with the recent introduction of this virus into the Western hemisphere. In particular, the occurrence of severe congenital infections and cases of Guillain-Barré syndrome has placed this virus squarely in the eyes of clinical and anatomic pathologists. This review article provides a basic introduction to ZIKV, its genetics, its structural characteristics, and its biology. A multidisciplinary effort will be essential to establish clinicopathologic correlations of the basic virology of ZIKV in order to advance development of diagnostics, therapeutics, and vaccines.

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era

PubMed Central

Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; Cheung, Leonard Y. M.; Daly, Alexandre Z.; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A. Bilge; Kitzman, Jacob O.; Mills, Ryan E.; Li, Jun Z.

2016-01-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD. PMID:27828722

[Research progress on the cloning of Mendel's gene in pea (Pisum sativum L.) and its application in genetics teaching].

PubMed

He, Feng-Hua; Zhu, Bi-Yan; Gao, Feng; Li, Shao-Shan; Li, Niang-Hui

2013-07-01

One hundred and fifty years ago, Gregor Mendel investigated the segregation of seven traits in pea (Pisum sativum) and established the law of segregation and the law of independent assortment in genetics. After the two laws of genetics were rediscovered in 1900, the seven traits have been extensively investigated in the fields of plant physiology and biochemistry as well as in the cell and molecular levels. Recently, with the development of molecular technology in genetics, four genes for seed shape (R), stem length (Le), cotyledon colour (I), and flower colour (A) have been cloned and sequenced; and another three genes for immature pod colour (Gp), fasciation (Fa) and pod form (V) have been located in the linkage groups, respectively. The identification and cloning of the four Mendel's genes will help deeply understand the basic concept of gene in many respects: like the diversity of gene function, the different origins for gene mutation in molecular level, and the molecular nature of a dominant gene or a recessive gene. In teaching of genetics, the introduction of most recent research advancements of cloning of Mendel's genes to the students and the interpretation of the Mendel's laws in molecular level will help students promote their learning interests in genetics and help students grasp the whole content from classical genetics to molecular genetics and the developmental direction of this subject.

Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

PubMed

Livshits, G; Yakovenko, K; Ginsburg, E; Kobyliansky, E

1998-01-01

The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

Solid organ transplants following hematopoietic stem cell transplant in children.

PubMed

Bunin, Nancy; Guzikowski, Virginia; Rand, Elizabeth R; Goldfarb, Samuel; Baluarte, Jorge; Meyers, Kevin; Olthoff, Kim M

2010-12-01

SOT may be indicated for a select group of pediatric patients who experience permanent organ failure following HSCT. However, there is limited information available about outcomes. We identified eight children at our center who received an SOT following an HSCT. Patients were six months to 18 yr at HSCT. Diseases for which children underwent HSCT included thalassemia, Wiskott-Aldrich syndrome, Shwachman-Diamond/bone marrow failure, sickle cell disease (SCD), erythropoietic porphyria (EP), ALL, chronic granulomatous disease, and neuroblastoma. Time from HSCT to SOT was 13 days to seven yr (median, 27 months. Lung SOT was performed for two patients with BO, kidney transplants for three patients, and liver transplants for three patients (VOD, chronic GVHD). Seven patients are alive with functioning allografts 6-180 months from SOT. Advances in organ procurement, operative technique, immunosuppressant therapy, and infection control may allow SOT for a select group of patients post-HSCT. However, scarcity of donor organs available in a timely fashion continues to be a limiting factor. Children who have undergone HSCT and develop single organ failure should be considered for an SOT if there is a high likelihood of cure of the primary disease. © 2010 John Wiley & Sons A/S.

Intermediate filament proteins of digestive organs: physiology and pathophysiology.

PubMed

Omary, M Bishr

2017-06-01

Intermediate filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the three major cytoskeletal protein families. Whether in digestive organs or other tissues, IFs share several unique features including stress-inducible overexpression, abundance, cell-selective and differentiation state expression, and association with >80 human diseases when mutated. Whereas most IF mutations cause disease, mutations in simple epithelial keratins 8, 18, or 19 or in lamin A/C predispose to liver disease with or without other tissue manifestations. Keratins serve major functions including protection from apoptosis, providing cellular and subcellular mechanical integrity, protein targeting to subcellular compartments, and scaffolding and regulation of cell-signaling processes. Keratins are essential for Mallory-Denk body aggregate formation that occurs in association with several liver diseases, whereas an alternate type of keratin and lamin aggregation occurs upon liver involvement in porphyria. IF-associated diseases have no known directed therapy, but high-throughput drug screening to identify potential therapies is an appealing ongoing approach. Despite the extensive current knowledge base, much remains to be discovered regarding IF physiology and pathophysiology in digestive and nondigestive organs. Copyright © 2017 the American Physiological Society.

[Factitious Disorder in Obstetrics: Case Report].

PubMed

Molano, Juan Carlos; Cortés, Natalia; Noguera, Efraín

2012-06-01

Munchhausen's syndrome is the best-studied type of factitious disorder with predominantly physical signs and symptoms. However, its clinical presentation during pregnancy is rare and literature on the subject is scarce. To present a case of factitious disorder during pregnancy. Review and analysis of a clinical case. The case of a 30-year-old woman six weeks pregnant who consults on multiple occasions with emesis and abdominal pain is discussed. Various different diagnoses were considered and pathologies such as acute intermittent porphyria, narcotic bowel syndrome, abdominal epilepsy, and esophageal spasm were discarded. The patient expressed her desire to terminate the pregnancy at week 21. The pregnancy was terminated after a medical panel concluded that there were both organic and mental conditions that placed the patient's health at risk. Factitious disorders are very complex and extremely challenging to the clinician especially during the initial phases. They are seldom suspected and rarely diagnosed even in hospital settings. Therefore it is of utmost importance to educate healthcare professionals in the detection of this disorder to ensure proper management and treatment. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Genetic identification and molecular modeling characterization reveal a novel PROM1 mutation in Stargardt4-like macular dystrophy

PubMed Central

Imani, Saber; Cheng, Jingliang; Shasaltaneh, Marzieh Dehghan; Wei, Chunli; Yang, Lisha; Fu, Shangyi; Zou, Hui; Khan, Md. Asaduzzaman; Zhang, Xianqin; Chen, Hanchun; Zhang, Dianzheng; Duan, Chengxia; Lv, Hongbin; Li, Yumei; Chen, Rui; Fu, Junjiang

2018-01-01

Stargardt disease-4 (STGD4) is an autosomal dominant complex, genetically heterogeneous macular degeneration/dystrophy (MD) disorder. In this paper, we used targeted next generation sequencing and multiple molecular dynamics analyses to identify and characterize a disease-causing genetic variant in four generations of a Chinese family with STGD4-like MD. We found a novel heterozygous missense mutation, c.734T>C (p.L245P) in the PROM1 gene. Structurally, this mutation most likely impairs PROM1 protein stability, flexibility, and amino acid interaction network after changing the amino acid residue Leucine into Proline in the basic helix-loop-helix leucine zipper domain. Molecular dynamic simulation and principal component analysis provide compelling evidence that this PROM1 mutation contributes to disease causativeness or susceptibility variants in patients with STGD4-like MD. Thus, this finding defines new approaches in genetic characterization, accurate diagnosis, and prevention of STGD4-like MD. PMID:29416601

Genetic instability in urinary bladder cancer: An evolving hallmark.

PubMed

Wadhwa, N; Mathew, B B; Jatawa, S K; Tiwari, A

2013-01-01

Bladder cancer is a major health-care concern. A successful treatment of bladder cancer depends on its early diagnosis at the initial stage. Genetic instability is an essential early step toward the development of bladder cancer. This instability is found more often at the chromosomal level than at the nucleotide level. Microsatellite and chromosomal instability markers can be used as a prognostic marker for screening bladder cancer. Bladder cancer can be distinguished in two different categories according to genetic instability: Cancers with chromosomal level instability and cancers with nucleotide level instability. Deoxyribonucleic acid (DNA) mismatch repair (MMR) system and its correlation with other biologic pathway, both are essential to understand the basic mechanisms of cancer development. Microsatellite instability occurs due to defects in DNA MMR genes, including human mutL homolog 1 and human mutL homolog 2. Chromosomal alterations including deletions on chromosome 3, 8, 9, 11, 13, 17 have been detected in bladder cancer. In the current review, the most recent literature of genetic instability in urinary bladder cancer has been summarized.

Genetics as a modernization program: biological research at the Kaiser Wilhelm Institutes and the political economy of the Nazi State.

PubMed

Gausemeier, Bernd

2010-01-01

During the Third Reich, the biological institutes of the Kaiser Wilhelm Society (KWG, Kaiser-Wilhelm-Gesellschaft) underwent a substantial reorganization and modernization. This paper discusses the development of projects in the fields of biochemical genetics, virus research, radiation genetics, and plant genetics that were initiated in those years. These cases exemplify, on the one hand, the political conditions for biological research in the Nazi state. They highlight how leading scientists advanced their projects by building close ties with politicians and science-funding organizations and companies. On the other hand, the study examines how the contents of research were shaped by, and how they contributed to, the aims and needs of the political economy of the Nazi system. This paper therefore aims not only to highlight basic aspects of scientific development under Nazism, but also to provide general insights into the structure of the Third Reich and the dynamics of its war economy.

Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain

PubMed Central

Florea, Michael; Hagemann, Henrik; Santosa, Gabriella; Micklem, Chris N.; Spencer-Milnes, Xenia; de Arroyo Garcia, Laura; Paschou, Despoina; Lazenbatt, Christopher; Kong, Deze; Chughtai, Haroon; Jensen, Kirsten; Freemont, Paul S.; Kitney, Richard; Reeve, Benjamin; Ellis, Tom

2016-01-01

Bacterial cellulose is a strong and ultrapure form of cellulose produced naturally by several species of the Acetobacteraceae. Its high strength, purity, and biocompatibility make it of great interest to materials science; however, precise control of its biosynthesis has remained a challenge for biotechnology. Here we isolate a strain of Komagataeibacter rhaeticus (K. rhaeticus iGEM) that can produce cellulose at high yields, grow in low-nitrogen conditions, and is highly resistant to toxic chemicals. We achieved external control over its bacterial cellulose production through development of a modular genetic toolkit that enables rational reprogramming of the cell. To further its use as an organism for biotechnology, we sequenced its genome and demonstrate genetic circuits that enable functionalization and patterning of heterologous gene expression within the cellulose matrix. This work lays the foundations for using genetic engineering to produce cellulose-based materials, with numerous applications in basic science, materials engineering, and biotechnology. PMID:27247386

Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster.

PubMed

Okada, Hirokazu; Ebhardt, H Alexander; Vonesch, Sibylle Chantal; Aebersold, Ruedi; Hafen, Ernst

2016-09-01

The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype-phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.

Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain.

PubMed

Florea, Michael; Hagemann, Henrik; Santosa, Gabriella; Abbott, James; Micklem, Chris N; Spencer-Milnes, Xenia; de Arroyo Garcia, Laura; Paschou, Despoina; Lazenbatt, Christopher; Kong, Deze; Chughtai, Haroon; Jensen, Kirsten; Freemont, Paul S; Kitney, Richard; Reeve, Benjamin; Ellis, Tom

2016-06-14

Bacterial cellulose is a strong and ultrapure form of cellulose produced naturally by several species of the Acetobacteraceae Its high strength, purity, and biocompatibility make it of great interest to materials science; however, precise control of its biosynthesis has remained a challenge for biotechnology. Here we isolate a strain of Komagataeibacter rhaeticus (K. rhaeticus iGEM) that can produce cellulose at high yields, grow in low-nitrogen conditions, and is highly resistant to toxic chemicals. We achieved external control over its bacterial cellulose production through development of a modular genetic toolkit that enables rational reprogramming of the cell. To further its use as an organism for biotechnology, we sequenced its genome and demonstrate genetic circuits that enable functionalization and patterning of heterologous gene expression within the cellulose matrix. This work lays the foundations for using genetic engineering to produce cellulose-based materials, with numerous applications in basic science, materials engineering, and biotechnology.

Online Mendelian Inheritance in Man (OMIM).

PubMed

Hamosh, A; Scott, A F; Amberger, J; Valle, D; McKusick, V A

2000-01-01

Online Mendelian Inheritance In Man (OMIM) is a public database of bibliographic information about human genes and genetic disorders. Begun by Dr. Victor McKusick as the authoritative reference Mendelian Inheritance in Man, it is now distributed electronically by the National Center for Biotechnology Information (NCBI). Material in OMIM is derived from the biomedical literature and is written by Dr. McKusick and his colleagues at Johns Hopkins University and elsewhere. Each OMIM entry has a full text summary of a genetic phenotype and/or gene and has copious links to other genetic resources such as DNA and protein sequence, PubMed references, mutation databases, approved gene nomenclature, and more. In addition, NCBI's neighboring feature allows users to identify related articles from PubMed selected on the basis of key words in the OMIM entry. Through its many features, OMIM is increasingly becoming a major gateway for clinicians, students, and basic researchers to the ever-growing literature and resources of human genetics. Copyright 2000 Wiley-Liss, Inc.

Neurocutaneous Disorders.

PubMed

Rosser, Tena

2018-02-01

This article presents an up-to-date summary of the genetic etiology, diagnostic criteria, clinical features, and current management recommendations for the most common neurocutaneous disorders encountered in clinical adult and pediatric neurology practices. The phakomatoses are a phenotypically and genetically diverse group of multisystem disorders that primarily affect the skin and central nervous system. A greater understanding of the genetic and biological underpinnings of numerous neurocutaneous disorders has led to better clinical characterization, more refined diagnostic criteria, and improved treatments in neurofibromatosis type 1, Legius syndrome, neurofibromatosis type 2, Noonan syndrome with multiple lentigines, tuberous sclerosis complex, Sturge-Weber syndrome, and incontinentia pigmenti. Neurologists require a basic knowledge of and familiarity with a wide variety of neurocutaneous disorders because of the frequent involvement of the central and peripheral nervous systems. A simple routine skin examination can often open a broad differential diagnosis and lead to improved patient care.

Research on optimization of combustion efficiency of thermal power unit based on genetic algorithm

NASA Astrophysics Data System (ADS)

Zhou, Qiongyang

2018-04-01

In order to improve the economic performance and reduce pollutant emissions of thermal power units, the characteristics of neural network in establishing boiler combustion model are analyzed based on the analysis of the main factors affecting boiler efficiency by using orthogonal method. In addition, on the basis of this model, the genetic algorithm is used to find the best control amount of the furnace combustion in a certain working condition. Through the genetic algorithm based on real number encoding and roulette selection is concluded: the best control quantity at a condition of furnace combustion can be combined with the boiler combustion system model for neural network training. The precision of the neural network model is further improved, and the basic work is laid for the research of the whole boiler combustion optimization system.

Generation of Infectious Poliovirus with Altered Genetic Information from Cloned cDNA.

PubMed

Bujaki, Erika

2016-01-01

The effect of specific genetic alterations on virus biology and phenotype can be studied by a great number of available assays. The following method describes the basic protocol to generate infectious poliovirus with altered genetic information from cloned cDNA in cultured cells.The example explained here involves generation of a recombinant poliovirus genome by simply replacing a portion of the 5' noncoding region with a synthetic gene by restriction cloning. The vector containing the full length poliovirus genome and the insert DNA with the known mutation(s) are cleaved for directional cloning, then ligated and transformed into competent bacteria. The recombinant plasmid DNA is then propagated in bacteria and transcribed to RNA in vitro before RNA transfection of cultured cells is performed. Finally, viral particles are recovered from the cell culture.

Overgrowth.

PubMed

Ambler, Geoffrey

2002-09-01

The predominant influences on fetal growth are maternal and placental factors. Post-natal growth is regulated by a complex interaction between genetic, environmental and hormonal influences. The role of the growth hormone insulin-like growth factor (GH-IGF) system is explored, including the emerging role of IGF-2 in fetal growth. Increasing understanding of the genetics of overgrowth and short stature syndromes is contributing greatly to basic understanding of growth regulation. A range of prenatal overgrowth syndromes is discussed, including those associated with neonatal hyperinsulinism and hypoglycaemia.Post-natal overgrowth may be caused by a diverse range of normal variant conditions, endocrine disorders, chromosomal abnormalities and other genetic syndromes. An approach to diagnosis is presented and major conditions discussed in detail. Sex-steroid therapy for height limitation continues to be a controversial area with uncertainty about height prediction, benefits achieved and possible long-term side-effects.

Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders--updated European recommendations.

PubMed

Dequeker, Els; Stuhrmann, Manfred; Morris, Michael A; Casals, Teresa; Castellani, Carlo; Claustres, Mireille; Cuppens, Harry; des Georges, Marie; Ferec, Claude; Macek, Milan; Pignatti, Pier-Franco; Scheffer, Hans; Schwartz, Marianne; Witt, Michal; Schwarz, Martin; Girodon, Emmanuelle

2009-01-01

The increasing number of laboratories offering molecular genetic analysis of the CFTR gene and the growing use of commercial kits strengthen the need for an update of previous best practice guidelines (published in 2000). The importance of organizing regional or national laboratory networks, to provide both primary and comprehensive CFTR mutation screening, is stressed. Current guidelines focus on strategies for dealing with increasingly complex situations of CFTR testing. Diagnostic flow charts now include testing in CFTR-related disorders and in fetal bowel anomalies. Emphasis is also placed on the need to consider ethnic or geographic origins of patients and individuals, on basic principles of risk calculation and on the importance of providing accurate laboratory reports. Finally, classification of CFTR mutations is reviewed, with regard to their relevance to pathogenicity and to genetic counselling.

Sleep and Development in Genetically Tractable Model Organisms

PubMed Central

Kayser, Matthew S.; Biron, David

2016-01-01

Sleep is widely recognized as essential, but without a clear singular function. Inadequate sleep impairs cognition, metabolism, immune function, and many other processes. Work in genetic model systems has greatly expanded our understanding of basic sleep neurobiology as well as introduced new concepts for why we sleep. Among these is an idea with its roots in human work nearly 50 years old: sleep in early life is crucial for normal brain maturation. Nearly all known species that sleep do so more while immature, and this increased sleep coincides with a period of exuberant synaptogenesis and massive neural circuit remodeling. Adequate sleep also appears critical for normal neurodevelopmental progression. This article describes recent findings regarding molecular and circuit mechanisms of sleep, with a focus on development and the insights garnered from models amenable to detailed genetic analyses. PMID:27183564

Genetic testing in congenital heart disease: A clinical approach

PubMed Central

Chaix, Marie A; Andelfinger, Gregor; Khairy, Paul

2016-01-01

Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel. PMID:26981213

Senior Computational Scientist | Center for Cancer Research

Cancer.gov

The Basic Science Program (BSP) pursues independent, multidisciplinary research in basic and applied molecular biology, immunology, retrovirology, cancer biology, and human genetics. Research efforts and support are an integral part of the Center for Cancer Research (CCR) at the Frederick National Laboratory for Cancer Research (FNLCR). The Cancer & Inflammation Program (CIP), Basic Science Program, HLA Immunogenetics Section, under the leadership of Dr. Mary Carrington, studies the influence of human leukocyte antigens (HLA) and specific KIR/HLA genotypes on risk of and outcomes to infection, cancer, autoimmune disease, and maternal-fetal disease. Recent studies have focused on the impact of HLA gene expression in disease, the molecular mechanism regulating expression levels, and the functional basis for the effect of differential expression on disease outcome. The lab’s further focus is on the genetic basis for resistance/susceptibility to disease conferred by immunogenetic variation. KEY ROLES/RESPONSIBILITIES The Senior Computational Scientist will provide research support to the CIP-BSP-HLA Immunogenetics Section performing bio-statistical design, analysis and reporting of research projects conducted in the lab. This individual will be involved in the implementation of statistical models and data preparation. Successful candidate should have 5 or more years of competent, innovative biostatistics/bioinformatics research experience, beyond doctoral training Considerable experience with statistical software, such as SAS, R and S-Plus Sound knowledge, and demonstrated experience of theoretical and applied statistics Write program code to analyze data using statistical analysis software Contribute to the interpretation and publication of research results

Microendophenotypes of psychiatric disorders: phenotypes of psychiatric disorders at the level of molecular dynamics, synapses, neurons, and neural circuits.

PubMed

Kida, S; Kato, T

2015-01-01

Psychiatric disorders are caused not only by genetic factors but also by complicated factors such as environmental ones. Moreover, environmental factors are rarely quantitated as biological and biochemical indicators, making it extremely difficult to understand the pathological conditions of psychiatric disorders as well as their underlying pathogenic mechanisms. Additionally, we have actually no other option but to perform biological studies on postmortem human brains that display features of psychiatric disorders, thereby resulting in a lack of experimental materials to characterize the basic biology of these disorders. From these backgrounds, animal, tissue, or cell models that can be used in basic research are indispensable to understand biologically the pathogenic mechanisms of psychiatric disorders. In this review, we discuss the importance of microendophenotypes of psychiatric disorders, i.e., phenotypes at the level of molecular dynamics, neurons, synapses, and neural circuits, as targets of basic research on these disorders.

Reporter Proteins in Whole-Cell Optical Bioreporter Detection Systems, Biosensor Integrations, and Biosensing Applications

PubMed Central

Close, Dan M.; Ripp, Steven; Sayler, Gary S.

2009-01-01

Whole-cell, genetically modified bioreporters are designed to emit detectable signals in response to a target analyte or related group of analytes. When integrated with a transducer capable of measuring those signals, a biosensor results that acts as a self-contained analytical system useful in basic and applied environmental, medical, pharmacological, and agricultural sciences. Historically, these devices have focused on signaling proteins such as green fluorescent protein, aequorin, firefly luciferase, and/or bacterial luciferase. The biochemistry and genetic development of these sensor systems as well as the advantages, challenges, and common applications of each one will be discussed. PMID:22291559

The use of fish models to study human neurological disorders.

PubMed

Matsui, Hideaki

2017-07-01

Small teleost fish including zebrafish and medaka have been used as animal models in basic science research due to the relative ease of handling and transparency during embryogenesis. Current advances in genetic engineering and progress in disease genetics allowed utilization of these fish to study neurological diseases and psychiatric disorders. This review summarizes the advantages and disadvantages of using fish for neuropsychiatric research using primarily our own studies as examples. We discuss how fish belong to a class of vertebrates, are feasible for imaging, and include diverse species with multiple research possibilities yet to be discovered. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Pathophysiology of chronic pancreatitis.

PubMed

Behrman, Stephen W; Fowler, Eric S

2007-12-01

Although the most common causes of chronic pancreatitis have not changed, it has become clear that a host of modifying biochemical, inflammatory, neural, and genetic deviations allows the disease to progress. Alterations in biochemical composition allow calcific stone formation, whereas various toxins, cytokines, and neuropeptides contribute to the progression of fibrosis and pain production. The basic cellular structure contributing to fibrosis of the pancreas has been elucidated and factors responsible for its activation delineated. Of most importance is the recent recognition of a set of genetic mutations that results in several aberrations of normal pancreatic physiology, which, in conjunction with other inciting insults or by themselves, allow the disease to begin and progress.

[Reflection of estimating postmortem interval in forensic entomology and the Daubert standard].

PubMed

Xie, Dan; Peng, Yu-Long; Guo, Ya-Dong; Cai, Ji-Feng

2013-08-01

Estimating postmortem interval (PMI) is always the emphasis and difficulty in forensic practice. Forensic entomology plays a significant indispensable role. Recently, the theories and technologies of forensic entomology are increasingly rich. But many problems remain in the research and practice. With proposing the Daubert standard, the reliability and accuracy of estimation PMI by forensic entomology need more demands. This review summarizes the application of the Daubert standard in several aspects of ecology, quantitative genetics, population genetics, molecular biology, and microbiology in the practice of forensic entomology. It builds a bridge for basic research and forensic practice to provide higher accuracy for estimating postmortem interval by forensic entomology.

From Green to Blue: Site-Directed Mutagenesis of the Green Fluorescent Protein to Teach Protein Structure-Function Relationships

ERIC Educational Resources Information Center

Giron, Maria D.; Salto, Rafael

2011-01-01

Structure-function relationship studies in proteins are essential in modern Cell Biology. Laboratory exercises that allow students to familiarize themselves with basic mutagenesis techniques are essential in all Genetic Engineering courses to teach the relevance of protein structure. We have implemented a laboratory course based on the…

Curing Hearing Loss: Patient Expectations, Health Care Practitioners, and Basic Science

ERIC Educational Resources Information Center

Oshima, Kazuo; Suchert, Steffen; Blevins, Nikolas H.; Heller, Stefan

2010-01-01

Millions of patients are debilitated by hearing loss, mainly caused by degeneration of sensory hair cells in the cochlea. The underlying reasons for hair cell loss are highly diverse, ranging from genetic disposition, drug side effects, traumatic noise exposure, to the effects of aging. Whereas modern hearing aids offer some relief of the symptoms…

Understanding a Basic Biological Process: Expert and Novice Models of Science.

ERIC Educational Resources Information Center

Kindfield, A. C. H.

1994-01-01

Reports on the meiosis models utilized by five individuals at each of three levels of expertise in genetics as each reasoned about this process in an individual interview setting. Results revealed a set of biologically correct features common to all individuals' models as well as a variety of model flaws (i.e., meiosis misunderstandings) which are…

Name that Gene: A Meaningful Computer-Based Genetics Classroom Activity that Incorporates Tolls Used by Real Research Scientists

ERIC Educational Resources Information Center

Wefer, Stephen H.

2003-01-01

"Name That Gene" is a simple classroom activity that incorporates bioinformatics (available biological information) into the classroom using "Basic Logical Alignment Search Tool (BLAST)." An excellent classroom activity involving bioinformatics and "BLAST" has been previously explored using sequences from bacteria, but it is tailored for college…

A Model System for the Study of Gene Expression in the Undergraduate Laboratory

ERIC Educational Resources Information Center

Hargadon, Kristian M.

2016-01-01

The flow of genetic information from DNA to RNA to protein, otherwise known as the "central dogma" of biology, is one of the most basic and overarching concepts in the biological sciences. Nevertheless, numerous studies have reported student misconceptions at the undergraduate level of this fundamental process of gene expression. This…

A Paper-and-Pencil Strategy for Teaching Mitosis and Meiosis, Diagnosing Learning Problems and Predicting Examination Performance.

ERIC Educational Resources Information Center

Mertens, Thomas R.; Walker, Julie O.

1992-01-01

Describes the Bajema strategy for teaching meiosis and how it is used in the general genetics course at Ball State University and can be used to identify students who have misconceptions of meiosis that can interfere with their learning the basics of Mendelian inheritance. (Contains 11 references.) (MDH)

Why You're You, Teacher's Edition. Probing the Natural World/3.

ERIC Educational Resources Information Center

Florida State Univ., Tallahassee. Dept. of Science Education.

The teacher's edition for the Intermediate Science Curriculum Study Level III unit entitled "Why You're You" provides specific suggestions for teaching the seven chapters included in the unit. The unit deals primarily with the concepts of genetics and a brief discussion is included in the beginning about some of the basic ideas in this…