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PubMed2004

High level of genetic diversity among spelt germplasm revealed by microsatellite markers.

The genetic diversity of spelt (Triticum aestivum (L.) Thell. subsp. spelta (L.) Thell.) cultivated presently is very narrow. Although the germplasm collections of spelt are extensive, the related genetic knowledge is often lacking and makes their use for genetic improvement difficult. The genetic diversity and structure of the spelt gene pool held in gene banks was determined using 19 simple sequence repeat (SSR) markers applied to 170 spelt accessions collected from 27 countries and 4 continents. The genetic distances (1 - proportion of shared alleles) were calculated and an unweighted pair-group method with arithmetic averaging (UPGMA)-based dendrogram was generated. The genetic diversity was high: 259 alleles were found and the mean interaccession genetic distance was 0.782 +/- 0.141. The dendrogram demonstrated the much higher genetic diversity of spelt held in germplasm collections than in the currently used genotypes. Accessions with the same geographical origin often tended to cluster together. Those from the Middle East were isolated first. All but one of the Spanish accessions were found in a unique subcluster. Most accessions from eastern Europe clustered together, while those from northwestern Europe were divided into two subclusters. The accessions from Africa and North America were not separated from the European ones. This analysis demonstrates the extent of genetic diversity of spelts held in germplasm collections and should help to widen the genetic basis of cultivated spelt in future breeding programs.

Alleles↗
PubMed2001

No evidence for a new variant of measles-mumps-rubella-induced autism.

OBJECTIVE: A link has been postulated between measles-mumps-rubella (MMR) vaccine and a form of autism that is a combination of developmental regression and gastrointestinal symptoms that occur shortly after immunization. This hypothesis has involved 3 separate claims: 1) that there is new phenotype of autism involving regression and gastrointestinal symptoms, 2) that this new variant is responsible for the alleged rise of autism rates, and 3) that this phenotype is associated with biological findings suggestive of the persistence of measles infection. We tested the first of these claims. If this new "autistic enterocolitis" syndrome had some validity, then 1 or several of the following 6 predictions should be supported by empirical data: 1) childhood disintegrative disorder has become more frequent, 2) the mean age of first parental concern for autistic children who are exposed to MMR is closer to the mean immunization age than in children who are not exposed to MMR, 3) regression in the development of children with autism has become more common in MMR-vaccinated children, 4) the age of onset for autistic children with regression clusters around the MMR immunization date and is different from that of autistic children without regression, 5) children with regressive autism have distinct symptom and severity profiles, and 6) regressive autism is associated with gastrointestinal symptoms and/or inflammatory bowel disorder. METHODS: Three samples were used. Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5 months) who were born between 1992 and 1995 and had a pervasive developmental disorder diagnosis as reported in a recent UK survey (post-MMR sample) were compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1 post-MMR [n = 68]) of autistic patients. All patients were assessed with the standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of age at first parental concerns and rates of regression across samples. Reliability was excellent on ADI scores, age of parental concern, and developmental regression. Furthermore, data on bowel symptoms and disorders were available in the epidemiologic survey from both pediatric and parental sources, and immunization dates were obtained from computerized records. RESULTS: The prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence interval: 0.02-3.6/10 000); this very low rate is consistent with previous estimates and is not suggestive of an increased frequency of this form of pervasive developmental disorder in samples of children who are immunized with MMR. There was no difference in the mean age at first parental concern between the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5 months). Thus, MMR immunization was not associated with a shift toward an earlier age for first parental concerns. Similarly, the rate of developmental regression reported in the post-MMR sample (15.6%) was not different from that in the pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the developmental course of autism had increased in frequency since MMR was introduced. In the epidemiologic sample, the subset of autistic children with regression had no other developmental or clinical characteristics, which would have argued for a specific, etiologically distinct phenotype. Parents of autistic children with developmental regression detected the first symptoms at a very similar age (19.8 months) to those of autistic children without regression (19.3 months). Moreover, the mean intervals from MMR immunization to parental recognition of autistic symptoms were comparable in autistic children with or without regression (248 vs 272 days; not significant). In the epidemiologic sample, gastrointestinal symptoms were reported in 18.8% of children. Constipation was the most common symptom (9.4%), and no inflammatory bowel disorder was reported. Furthermore, there was no association between developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95% confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample experienced both problems, a rate that did not exceed chance expectations. CONCLUSIONS: No evidence was found to support a distinct syndrome of MMR-induced autism or of "autistic enterocolitis." These results add to the recent accumulation of large-scale epidemiologic studies that all failed to support an association between MMR and autism at population level. When combined, the current findings do not argue for changes in current immunization programs and recommendations.

Age of Onset↗
PubMed2002

Genetic and environmental parameters for steer ultrasound and carcass traits.

Carcass measurements for weight, longissimus muscle area, 12-13th-rib fat thickness, and marbling score, as well as for live animal measurements of weight at the time of ultrasound, ultrasound longissimus muscle area, ultrasound 12-13th-rib fat thickness, and ultrasound-predicted percentage ether extract were taken on 2,855 Angus steers. The average ages for steers at the time of ultrasound and at slaughter were 391 and 443 d, respectively. Genetic and environmental parameters were estimated for all eight traits in a multivariate animal model. In addition to a random animal effect, the model included a fixed effect for contemporary group and a covariate for measurement age. Heritabilities for carcass weight, carcass longissimus muscle area, carcass fat thickness, carcass marbling score, ultrasound weight, ultrasound longissimus muscle area, ultrasound fat thickness, and ultrasound-predicted percentage ether extract were 0.48, 0.45, 0.35, 0.42, 0.55, 0.29, 0.39, and 0.51, respectively. Genetic correlations between carcass and ultrasound longissimus muscle area, carcass and ultrasound fat thickness, carcass marbling score and ultrasound-predicted percentage ether extract, and carcass and ultrasound weight were 0.69, 0.82, 0.90, and 0.96, respectively. Additional estimates were derived from a six-trait multivariate animal model, which included all traits except those pertaining to weight. This model included a random animal effect, a fixed effect for contemporary group, as well as covariates for both measurement age and weight. Heritabilities for carcass longissimus muscle area, carcass fat thickness, carcass marbling score, ultrasound longissimus muscle area, ultrasound fat thickness, and ultrasound-predicted percentage ether extract were 0.36, 0.39, 0.40, 0.17, 0.38, and 0.49, respectively. Genetic correlations between carcass and ultrasound longissimus muscle area, carcass and ultrasound fat thickness, and carcass marbling and ultrasound-predicted percentage ether extract were 0.58, 0.86, and 0.94, respectively. The high, positive genetic correlations between carcass and the corresponding real-time ultrasound traits indicate that real-time ultrasound imaging is an alternative to carcass data collection in carcass progeny testing programs.

Adipose Tissue↗
PubMed2025

Genomic prediction-aided incorporation of genetic resources into elite breeding: lessons from a collaborative multiparental design in flint maize.

A public private cooperative mating design between elite maize inbred lines and diversity donors shows that genomic prediction holds great promise to improve the use of genetic resources. Genetic diversity is essential for plant breeding, enabling long-term gains and adaptation to climate change and new agronomical practices. Breeders can access diverse genetic resources to enhance elite germplasm and introduce new favorable variations. The limited performance of genetic resources may hamper their use. To overcome this, a bridging population can be implemented to evaluate and select progenies from crosses between diversity donors and elite lines before their introduction in breeding programs. The choice of such crosses can be dealt with the usefulness criterion (UC), which determines its ability to produce transgressive individuals. This paper investigates the use of genome-wide marker effects to predict (i) the performance of individuals derived from crosses between donors and elite lines and (ii) the UC of crosses not observed yet. It also compares donor introduction strategies based on the UC or the H criterion, which considers the genome-wide donor-elite complementarity. We used a flint maize collaborative multi-parental BC1-S2 population, consisting in materials from six breeding companies and one public institute crossed to different donors. The 20 crosses had contrasted means and genetic variances, and most of them presented transgressive individuals above the elite parent. Results emphasize the importance of half-siblings derived from the elite line parent of the predicted cross to efficiently predict progeny performances or the UC. They also showed that using the H criterion appears promising to select iteratively donors that best complement initial elite materials. The paper concludes with guidelines for implementing a bridging population using genome-wide marker-based predictions.

Zea mays↗
PubMed2004

A history of medical genetics in pediatrics.

Medical genetics emerged from a basic science only one half century ago. Scientists and physicians housed in a variety of basic science and clinical departments have accomplished many of the major advances in the study of genetic diseases in children. A scientific approach to human genetics emerged in 1948 with the establishment of the American Society of Human Genetics. Even before the use of modern laboratory techniques, Pediatric departments spearheaded the clinical description of simple genetic disorders, syndromes, and major malformations. The burgeoning of medical genetics as a specialty and its tremendous growth in departments of pediatrics was stimulated by major technological advances, such as the ability to visualize human chromosomes, the development of methods to study biochemical variations in blood and urine, cell culture, somatic cell hybridization, and molecular technology, all of which allowed for the diagnosis, treatment, and prevention of genetic disorders in children. Many pediatricians sought training in genetics, and training programs in medical genetics flourished in departments of pediatrics. The explosion of knowledge concerning the metabolic and molecular causes of genetic disease and understanding of their pathogenesis has led to a variety of specific diagnostic, preventive, and therapeutic approaches for alleviating the symptoms or preventing the complications of many of these disorders. Medical genetics is now recognized as a distinct medical specialty with its own American Board of Medical Specialties approved board (American Board of Medical Genetics) and clinical specialty college (American College of Medical Genetics).

Child↗
PubMed2007

Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone.

CONTEXT: The common P12A polymorphism in PPARG (a target for thiazolidinedione medications) has been consistently associated with type 2 diabetes. OBJECTIVE: We examined whether PPARG P12A affects progression from impaired glucose tolerance to diabetes, or responses to preventive interventions (lifestyle, metformin, or troglitazone vs. placebo). PATIENTS: This study included 3548 Diabetes Prevention Program participants. DESIGN: We performed Cox regression analysis using genotype at PPARG P12A, intervention, and their interactions as predictors of diabetes incidence. We also genotyped five other PPARG variants implicated in the response to troglitazone and assessed their effect on insulin sensitivity at 1 yr. RESULTS: Consistent with prior cross-sectional studies, P/P homozygotes at PPARG P12A appeared more likely to develop diabetes than alanine carriers (hazard ratio, 1.24; 95% confidence interval, 0.99-1.57; P=0.07) with no interaction of genotype with intervention. There was a significant interaction of genotype with body mass index and waist circumference (P=0.03 and 0.002, respectively) with the alanine allele conferring less protection in more obese individuals. Neither PPARG P12A nor five other variants significantly affected the impact of troglitazone on insulin sensitivity in 340 participants at 1 yr. CONCLUSIONS: The proline allele at PPARG P12A increases risk for diabetes in persons with impaired glucose tolerance, an effect modified by body mass index. In addition, PPARG P12A has little or no effect on the beneficial response to troglitazone.

Amino Acid Substitution↗
PubMed2004

Quantitative trait loci (QTL) detection in multicross inbred designs: recovering QTL identical-by-descent status information from marker data.

Mapping quantitative trait loci in plants is usually conducted using a population derived from a cross between two inbred lines. The power of such QTL detection and the parameter estimates depend largely on the choice of the two parental lines. Thus, the QTL detected in such populations represent only a small part of the genetic architecture of the trait. In addition, the effects of only two alleles are characterized, which is of limited interest to the breeder, while common pedigree breeding material remains unexploited for QTL mapping. In this study, we extend QTL mapping methodology to a generalized framework, based on a two-step IBD variance component approach, applicable to any type of breeding population obtained from inbred parents. We then investigate with simulated data mimicking conventional breeding programs the influence of different estimates of the IBD values on the power of QTL detection. The proposed method would provide an alternative to the development of specifically designed recombinant populations, by utilizing the genetic variation actually managed by plant breeders. The use of these detected QTL in assisting breeding would thus be facilitated.

Computer Simulation↗
PubMed1994

The origins and consequences of genetic instability in prokaryotes.

The causes of genetic change include errors in replication and repair, transposition and recombination. Together, these processes generate a reservoir of genetic variants from which selection will amplify any changes which increase host fitness. Recombination, transposition and slippage during replication may all result in large-scale DNA rearrangements. Homologous and illegitimate recombination generate deletions, inversions, duplications and fusions. Intramolecular transposition can cause deletion or inversion of DNA sequences adjacent to the mobile element, while intermolecular movement may lead to fusion of donor and target replicons when transposition is replicative. Of crucial importance is how genetic variation affects the fitness of the host cell. For a neutral variant the probability of eventual fixation is small, but changes which increase host cell fitness pose a more serious problem because these cells will eventually dominate the culture. The most effective way to combat the proliferation of variant plasmid cloning vectors is to block the processes by which they arise. Cloning vectors should be "stress-tested" and DNA sequence analysis programs can be used to screen for sequence repetition which should be removed, as far as possible, from both vectors and cloned sequences. It is also important that vectors place modest metabolic demands on their hosts in order to minimise the potential increase in fitness associated with changes in plasmid structure.

Biotechnology↗
PubMed1998

Genetic variability in the area searched by a parasitic wasp: analysis from automatic video tracking of the walking path.

The ability of foraging hymenopterous parasitoid females to discover their hosts, and thus to be efficient agents in biological control programs, is likely to be related to the surface they are able to prospect per unit of time. However, this behavioural trait has never been accurately estimated, and its implication in female efficiency has never been really demonstrated. This paper provides an algorithmic method that can be used to estimate this trait from an automatic recording of the females' walking path. Using stochastic procedures simulating walking tracks, this trait is shown to be strongly related to the number of hosts that parasitoid females are able to attack per unit of time. This trait was estimated for individual females of Trichogramma brassicae Bezdenko (Hymenoptera; Trichogrammatidae). On average, females of this species are able to prospect about 28mm(2)s(-1). Finally, the genetic variation in this trait was studied using the iso-female line method. A significant genetic variability was observed. It provides the basic information that is necessary to start a genetic selection of mass-reared Trichogramma in order to improve their efficiency in controlling target pests in biological control programs. The functional and evolutionary implications of these results are discussed.

Journal Article↗
PubMed1983

The frequency among Japanese of heterozygotes for deficiency variants of 11 enzymes.

Eleven human enzymes, chosen for this study because of relatively small coefficients of variation for mean activity, have been surveyed for the frequency with which activities less than or equal to 66% of the mean value occur. This criterion should detect almost all heterozygotes for variants lacking any activity plus a fraction of the persons with variants characterized by markedly depressed activity and/or instability. The enzymes surveyed are TPI, PGK, AK1, LDH, GAPD, GPI, PK, 6PGD, G6PD, GOT1, and HK. The number of determinations per enzyme ranged from 310 to 3,173, for a total of 26,634 determinations. Family studies have thus far been possible in 52 instances in which the initial observation of activity less than or equal to 66% of normal was confirmed. In every instance, a parent exhibited a similar finding, giving confidence that a true genetic entity was being detected. With this approach, the frequency of heterozygotes per 1,000 determinations varied from 0.0 (AK1, 6PGD) to 13.8 (PK), with an average of 2.4. For these same systems, in this laboratory the frequency of "rare" electrophoretic variants is 2.3/1,000, the ratio of the latter to the former thus being 1.0 in Japanese. Our experience with these deficiency phenotypes to date suggests that for selected enzymes such phenotypes can be incorporated into a program designed to detect mutational events.

Enzymes↗
PubMed1999

Analysis of the mouse proteome. (I) Brain proteins: separation by two-dimensional electrophoresis and identification by mass spectrometry and genetic variation.

The total protein of the mouse brain was fractionated into three fractions, supernatant, pellet extract and rest pellet suspension, by a procedure that avoids any loss of groups or classes of proteins. The supernatant proteins were resolved to a maximum by large-gel two-dimensional electrophoresis. Two-dimensional patterns from ten individual mice of the commonly used inbred strain C57BL/6 (species: Mus musculus) were prepared. The master pattern was subjected to densitometry, computer-assisted image analysis and treatment with our spot detection program. The resulting two-dimensional pattern, a standard pattern for mouse brain supernatant proteins, was divided into 40 squares, calibrated, and specified by providing each spot with a number. The complete pattern and each of the 40 squares are shown in our homepage (http://www.charite.de/ humangenetik). The standard pattern comprises 8767 protein spots. To identify the proteins known so far in the brain fraction investigated, a first set of 200 spots was analyzed by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) after in-gel digestion. By screening protein databases 115 spots were identified; by extending the analysis to selected, genetically variant protein spots, 166 spots (including some spot series) were identified in total. This number was increased to 331 by adding protein spots identified indirectly by a genetic approach. By comparing the two-dimensional patterns from C57BL/6 mice with those of another mouse species (Mus spretus), more than 1000 genetically variant spots were detected. The genetic analysis allowed us to recognize spot families, i.e., protein spots that represent the same protein but that are post-translationally modified. If some members of the family were identified, the whole family was considered as being identified. Spot families were investigated in more detail, and interpreted as the result of protein modification or degradation. Genetic analysis led to the interesting finding that the size of spot families, i.e., the extent of modification or degradation of a protein, can be genetically determined. The investigation presented is a first step towards a systematic analysis of the proteome of the mouse. Proteome analysis was shown to become more efficient, and, at the same time, linked to the genome, by combining protein analytical and genetic methods.

Animals↗
PubMed2004

Developmental shift in bidirectional functions of taurine-sensitive chloride channels during cortical circuit formation in postnatal mouse brain.

Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in the developing mammalian cerebral cortex, however, few studies have reported its neurobiological functions during development. In this study, by means of whole-cell patch-clamp recordings, we examined the effects of taurine on chloride channel receptors in neocortical neurons from early to late postnatal stages, which cover a critical period in cortical circuit formation. We show here that taurine activates chloride channels in cortical neurons throughout the postnatal stages examined (from postnatal day 2 to day 36). The physiological effects of taurine changed from excitatory to inhibitory due to variations in the intracellular Cl- concentration during development. An antagonist blocking analysis also demonstrated a developmental shift in the receptor target of taurine, from glycine receptors to GABAA receptors. Taken together, these results may reflect genetically programmed, bidirectional functions of taurine. At the early developmental stage, taurine acting on glycine receptors would serve to promote cortical circuit formation. As cortical circuit has to be regulated in the later stages, taurine would serve as a safeguard against hyperexcitable circuit.

Aging↗
PubMed2004

Metabolic control analysis as a mechanism that conserves genetic variance during advanced cycle breeding.

The recycling of elite inbreds (i.e., advanced cycle breeding) has led to significant genetic gains but also to a narrow gene pool in plant breeding programs. Sustained yield improvements in many crops have suggested that genetic variance is not depleted at a rate predicted by an additive genetic model. Unlike the additive model in classical quantitative genetic theory, metabolic control analysis relates the variation in a biochemical process with the genetic variation in a quantitative trait. Our objective was to determine whether metabolic control analysis is a mechanism that slows the decrease in genetic variance during advanced cycle breeding. Three cycles of advanced cycle breeding were simulated with 10, 50, or 100 quantitative trait loci (QTL) controlling a trait. In metabolic control analysis, these QTL coded for enzymes involved in a linear metabolic pathway that converted a substrate into a product. In the absence of selection, both the additive model and the metabolic control analysis model led to about a 50% reduction in genetic variance from cycle to cycle. With selection, the additive model led to a 50-58% reduction in genetic variance, but the metabolic control analysis model generally led to only a 12-54% reduction. We suggest selection in a metabolic control analysis model as a mechanism that slows the decrease in genetic variance during advanced cycle breeding. This conservation of genetic variance would allow breeders to achieve genetic gains for a longer period than expected under the additive model.

Conserved Sequence↗
PubMed2005

Genetic variability and genetic structure of wild and semi-domestic populations of tasar silkworm (Antheraea mylitta ) ecorace Daba as revealed through ISSR markers.

The genetic diversity in the wild and semi-domestic populations of Daba ecorace of Antheraea mylitta was studied to ascertain the distribution of variability within and among populations of semi-domestic bivoltine (DB), trivoltine (DT) and nature grown wild populations (DN) with inter-simple sequence repeat (ISSR) markers. A total of 138 markers were produced among 56 individuals of the three populations, of which 98% were polymorphic. For the individual populations, the percentage polymorphism was 58.69, 52.9 and 77.54 for DB, DT and DN, respectively. Average number of observed (1.791+/- 0.408) and effective alleles (1.389+/-0.348) was also high in the wild populations in comparison to the bivoltine and trivoltine semi-domestic populations. Genetic diversity (H(t)) in DB, DT and DN was 0.180+/- 0.033, 0.153+/- 0.032 and 0.235+/- 0.033, respectively and within-population genetic diversity (H(s)) ranged from 0.166 to 0.259 with a mean of 0.189. Mean gene differentiation (G(ST)) was found to be 0.25. Shanon's diversity index was 0.278, 0.237 and 0.361 for DB, DT and DN and overall it was 0.391. Gene flow (N(m)) among the populations was 1.509. The dendrogram produced by UPGMA with Dice's genetic distance matrices resulted in the formation of three major clusters separating the three populations. Considerable intra- and inter-population variability is found in all three populations. The population structure analysis further suggests that the semi-domestic populations of Daba ecorace are at the threshold of differentiating themselves. The high genetic variability present within wild Daba population of A. mylitta is of much importance for conservation as well as utilization in systematic breeding program.

Alleles↗
PubMed1997

Vaccine design, evaluation, and community-based use for antigenically variable infectious agents.

A major challenge for vaccine design and development, and for trials of new vaccines, is to tackle antigenically variable infectious agents. Here we outline a few general conceptual issues and then discuss new frameworks that are being developed to help understand how vaccination might change the distribution, abundance, and type of strains in a population. Herd Immunity is a key concept in population-based immunisation programmes and has to be considered in vaccine design and use even though it may cause a conflict between the needs of the individual versus those of the community. This issue is of increasing importance since once common infections are becoming rare due to effective vaccination. Concomitantly, adverse effects arising from immunisation are becoming more apparent as infection-induced morbidity declines to very low levels. Efficacy is widely regarded as a key criterion in vaccine design but duration of protection is of equal importance. Whether it is possible to produce effective vaccines to antigenically diverse pathogens remains uncertain but progress towards this goal will be enhanced by a better understanding of the population genetics of the target infectious agent facilitated by molecular epidemiological studies to assess the genetic constitution of pathogen populations and changes therein over time.

Antigenic Variation↗
PubMed2000

Isozyme diversity in cassava cultivars (Manihot esculenta Crantz).

Isoenzyme electrophoresis was used as a method to determine genetic diversity in various M. esculenta cultivars collected in the Southwestern (SW) and Northwestern (NW) regions of the State of Parana, in the South region of Brazil, and in cultivars produced at the Agronomic Institute of Campinas (IAC), São Paulo State, Southeastern region of Brazil. The cultivars have been maintained by vegetative propagation for 5 years and are useful in production programs. A total of 28 loci in the acid phosphatase (ACP; EC 3.1.3.2), esterases (EST; EC 3.1.1.1), malate dehydrogenase (MDH; EC 1.1.1.37), and shikimate dehydrogenase (SKDH; EC 1.1.1.15) isozymes was analyzed. The proportion of polymorphic loci for NW, SW, and IAC cultivars was 57.14, 50.0, and 53.6% respectively. Genetic diversity calculated by Nei's genetic identity (I) showed high I values for the three M. esculenta subpopulations. The high degree of polymorphism expressed by cassava cultivars is highly relevant to stimulate breeding programs with M. esculenta species.

Alleles↗
PubMed1988

Developmental characterization and chromosomal mapping of the 5-azacytidine-sensitive fluF locus of Aspergillus nidulans.

In Aspergillus nidulans, a fungus that possesses negligible, if any, levels of methylation in its genome, low concentrations of 5-azacytidine (5-AC) convert a high percentage of the cell population to fluffy phenotypic variants through a heritable modification of a single nuclear gene (M. Tamame, F. Antequera, J. R. Villanueva, and T. Santos, Mol. Cell. Biol. 3:2287-2297, 1983). This new 5-AC-altered locus, designated here fluF1, was mapped as the closest marker to the centromere that has been identified so far on the right arm of chromosome VIII. Of all mutagens tested, only 5-AC induced the fluffy phenotype with a significant frequency. Furthermore, we determined that the wild-type, dominant allele of the fluF gene was primarily accessible to modification by 5-AC at the initial stages of fungal vegetative growth. These results indicated that 5-AC does not act through random mutagenic action but, rather, that fluF constitutes a specific target for this drug during a well-defined period of fungal development. Alteration of fluF by 5-AC resulted in a dramatic modification of the developmental program of A. nidulans. The resulting fluffy clones were characterized by massive, uncontrolled proliferation of undifferentiated hyphae, a drastic delay in the onset of asexual differentiation (conidiation), and colonies with an invasive nature. These features are reminiscent of the malignant properties of tumor cells. We propose that the locus fluF plays a primary role in the control of cell proliferation in A. nidulans and that its alteration by 5-AC produces pleiotropic modifications of the developmental program of this fungus.

Aspergillus nidulans↗
PubMed2001

National Institutes of Health Consensus Development Conference Statement: phenylketonuria: screening and management, October 16-18, 2000.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding screening for and management of phenylketonuria (PKU). PARTICIPANTS: A nonfederal, nonadvocate, 14-member panel representing the fields of pediatrics, genetics, human development, public policy, nursing, and molecular physiology and including patient representatives. In addition, 19 experts in pediatrics, medical genetics, psychology, pediatric neurology, biochemical and molecular genetics, and gene therapy presented data to the panel and to a conference audience of 312. EVIDENCE: The literature was searched using Medline for January 1980 through July 2000, and an extensive bibliography of 3394 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. CONCLUSIONS: Genetic testing for PKU has been in place for almost 40 years and has been very successful in preventing severe mental retardation in thousands of children and adults. Metabolic control is necessary across the lifespan of individuals with PKU. A comprehensive, multidisciplinary, integrated system is needed to delivery of care to individuals with PKU. Greatly needed are consistency and coordination between screening, treatment, data collection, and patient support programs. There should be equal access to culturally sensitive, age-appropriate treatment programs. Ethically sound, specific policies for storage, ownership, and use in future studies of archived samples remaining from PKU testing should be established. Research into the pathophysiology of PKU and relationship to genetic, neural, and behavioral variation is strongly encouraged. Uniform policies must be established to remove financial barriers to the acquisition of medical foods and modified low-protein foods and to provide access to support services needed to maintain metabolic control in individuals with PKU. Research on nondietary alternative treatments for PKU is strongly encouraged. To achieve optimal statistical power and cross-cultural applicability, it will be beneficial to use data acquired via national and international collaboration.phenylketonuria, hyperphenylalanimea, phenylketonuria screening, phenylalanine-restricted diet, maternal phenylketonuria, newborn screening, phenylalanine monitoring, phenylketonuria outcomes.

Adult↗