Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “programmed genetic variation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMedDate not supplied

A method for the dynamic management of genetic variability in dairy cattle.

According to the general approach developed in this paper, dynamic management of genetic variability in selected populations of dairy cattle is carried out for three simultaneous purposes: procreation of young bulls to be further progeny-tested, use of service bulls already selected and approval of recently progeny-tested bulls for use. At each step, the objective is to minimize the average pairwise relationship coefficient in the future population born from programmed matings and the existing population. As a common constraint, the average estimated breeding value of the new population, for a selection goal including many important traits, is set to a desired value. For the procreation of young bulls, breeding costs are additionally constrained. Optimization is fully analytical and directly considers matings. Corresponding algorithms are presented in detail. The efficiency of these procedures was tested on the current Norman population. Comparisons between optimized and real matings, clearly showed that optimization would have saved substantial genetic variability without reducing short-term genetic gains.

Animals↗
PubMed1998

Restriction digest of PCR-amplified mtDNA from fin clips is an assay for sequence genetic "tags" among hundreds of fish in wild populations.

We tested the feasibility of recovering from wild populations mitochondrial DNA genetic "tags" that might result from release of hatchery-reared fingerlings for marine stock enhancement. A practical, nondestructive method of genetic "tag" recovery would allow quantitative assessment of the efficacy of such programs. A rare mtDNA variant with two sites each instead of one for TaqI and RsaI in the control region was used as a mock genetic "tag" in snook (Centropomus undecimalis). We assayed for the variant among nearly 900 fish by restriction digests of DNA amplified by polymerase chain reaction (PCR) obtained from fin-clip extracts, finding only a single second example of the variant. Thus, mtDNA "tags" can be nondestructively assayed for with specificity among hundreds of individuals.

Animals↗
PubMed1999

Two-dimensional gene scanning: exploring human genetic variability.

Current methods for mutation detection are not optimized for the generation of highly accurate data on multiple genes of hundreds of individuals in population-based studies. Two-dimensional gene scanning (TDGS) is a high-resolution system for detecting mutational variants in multiple genes in parallel. TDGS is based on a combination of extensive multiplex polymerase chain reaction (PCR) and two-dimensional (2-D) DNA electrophoresis. The latter involves a size separation step followed by denaturing gradient gel electrophoresis (DGGE). TDGS tests for a number of large human disease genes have been designed, using a computer program to optimally position PCR primers around the relevant target sequences (e.g., exons) and evaluated using panels of samples with previously detected mutations. The results indicate a high sensitivity and specificity, equal to nucleotide sequencing, which is generally considered as the gold standard. Here, we describe the different components of the TDGS process and its potential application as a high-throughput system for the systematic identification of human gene variants.

Automation↗
PubMed1988

An interactive computer program for the analysis of HLA class II restriction fragment patterns.

There is considerable current interest in the application of Southern blotting and hybridization, with locus-specific HLA class II probes, to HLA typing. The work of several laboratories has shown that, under suitable conditions, restriction fragment patterns that correlate with DR and DQ serology and with DP cellular reactivities can be obtained from homozygous cell lines. Although the identification of class II specificities from restriction fragment patterns is relatively straightforward in homozygotes, the increased complexity of the patterns obtained from heterozygotes makes the interpretation considerably more difficult; this difficulty is compounded by even slight variation between and within gels. We have developed an interactive computer program that allows HLA-DR and DQ typing by the visual matching of restriction fragment pattern data with standard data derived from a panel of well-characterized homozygous cell lines. The program also uses a simple algorithm (after Southern) to estimate the fragment sizes in the unknown track. The screen display can be printed out to give a convenient record of the match; a numerical measure is also given of the goodness of fit of the new data.

Algorithms↗
PubMed2004

High-throughput mitochondrial genome screening method for nonmelanoma skin cancer using multiplexed temperature gradient capillary electrophoresis.

BACKGROUND: We explored the utility of multiplexed temperature gradient capillary electrophoresis (TGCE) as a screening tool for identifying genetic changes in the human mitochondrial genome. We examined changes in mitochondrial DNA (mtDNA) in nonmelanoma skin cancers (NMSCs), using TGCE to resolve genetic differences contained within the tumors compared with the control DNA. METHODS: The entire mtDNA from NMSC tissue samples was amplified in 17 overlapping amplicons averaging 1.1 kb in size. Fourteen of these amplicons were digested with restriction endonucleases into as many as five smaller analyzable fragments. Digested tumor mtDNA amplicons were annealed with digested amplicons from the control DNA to form heteroduplexes in regions of DNA mismatch. TGCE was performed in a 96-well parallel format to detect mtDNA changes in a high-throughput fashion. RESULTS: TGCE resolved heteroduplexes from homoduplexes in singlet reactions and in multiplexed assays. Using a single programmed temperature gradient, we detected 18 of 20 mtDNA changes contained within the specimens. This system was also able to detect a single nucleotide change in a fragment as large as 2 kb. CONCLUSION: Multiplexed TGCE is a sensitive and high-throughput screening tool for identifying mtDNA variations.

Base Sequence↗
PubMed1993

Hb Val de Marne [alpha 133(H16)Ser-->Arg]: a new hemoglobin variant with moderate increase in oxygen affinity.

Hb Val de Marne [alpha 133(H16)Ser-->Arg] was found in a French family during a neonatal hemoglobinopathy screening program. The abnormal hemoglobin was found, within a few months interval, in two newborn children who were first cousins. In the children as well as in the parents carrying this hemoglobin variant, the red cell parameters were normal. Hb Val de Marne, isolated by isoelectrofocusing, displayed a slightly higher auto-oxidation rate than Hb A. Its oxygen affinity was increased 1.7-fold in comparison to that of Hb A. The heterotropic effects were normal.

Adult↗
PubMed1993

Report on a workshop to examine methods to arrive at risk estimates for radiation-induced cancer in the human based on laboratory data. Jointly sponsored by the Office of Health and Energy Research, Department of Energy, and Columbia University.

This summary is a record of discussions and the general consensus reached by the participants. The views expressed are those of the attending scientists and do not necessarily represent the policy or opinion of the Department of Energy. An urgent need is recognized for better estimates of the risk of cancer from low levels of radiation. This need arises because of the ongoing nuclear energy option, the hazard of naturally occurring radon, and the possibility of an increasing number of lawsuits by individuals exposed to radiation in the past. The most recent estimates of risk evaluated by UN-SCEAR and BEIR V rely heavily on epidemiological studies of the A-bomb survivors which have recognized limitations and cannot provide direct risk information for chronic low-dose-rate exposure such as that experienced in occupational and medical settings. It was the consensus view that an effort to obtain information relative to risk estimates for radiation-induced cancer in humans, based on laboratory data, would be both important and timely: important, because of the opportunity to extend existing epidemiological data and overcome existing limitations; and timely, because of advances in cellular and molecular biology. In the short term, such an effort could supplement epidemiological data by providing information on the variation of cancer risk estimates with radiation dose rate and radiation quality and by providing guidance on the extrapolation of data measured at high doses to low dose regions where direct measurements are not feasible. In the long term, it may be possible to use new information about the genome from cellular and molecular studies to refine epidemiological data, i.e., to integrate classical epidemiological approaches with cell and animal biology as well as molecular genetics. Laboratory-based studies may be able to supplement epidemiological studies by: (1) identifying the molecular lesions involved in radiation-induced cancer and resolving dose, dose-rate, and radiation quality effects on their repair; (2) suggesting more biologically realistic models to describe cancer induction; and (3) addressing the problem of individual susceptibility to radiation effects and identifying radiosensitive and/or radioresistant subpopulations. It is appropriate and timely that the DOE develop and fund a research program to target areas where laboratory data are required to supplement the epidemiological cancer risk estimates. Broad-based support will be necessary for research in many fields where efforts are already ongoing, with special focus on two newer areas: attempts to understand individual susceptibility to radiation effects, and the development of model systems to investigate the mechanisms of radiation carcinogenesis.

Disease Susceptibility↗
PubMed2004

SNP2CAPS: a SNP and INDEL analysis tool for CAPS marker development.

With the influx of various SNP genotyping assays in recent years, there has been a need for an assay that is robust, yet cost effective, and could be performed using standard gel-based procedures. In this context, CAPS markers have been shown to meet these criteria. However, converting SNPs to CAPS markers can be a difficult process if done manually. In order to address this problem, we describe a computer program, SNP2CAPS, that facilitates the computational conversion of SNP markers into CAPS markers. 413 multiple aligned sequences derived from barley ESTs were analysed for the presence of polymorphisms in 235 distinct restriction sites. 282 (90%) of 314 alignments that contain sequence variation due to SNPs and InDels revealed at least one polymorphic restriction site. After reducing the number of restriction enzymes from 235 to 10, 31% of the polymorphic sites could still be detected. In order to demonstrate the usefulness of this tool for marker development, we experimentally validated some of the results predicted by SNP2CAPS.

Base Sequence↗
PubMed1995

Egg fluids and cells of the chorioallantoic membrane of embryonated chicken eggs can select different variants of influenza A (H3N2) viruses.

Growth of influenza viruses in embryonated eggs frequently results in the selection of virus variants with amino acid changes near the receptor-binding pocket of the hemagglutinin molecule, yet the mechanism by which this third form of influenza variation occurs (the other two being antigenic drift and shift) has not been clearly defined. Because egg-mediated variation might affect influenza vaccine and surveillance programs, we have initiated studies to determine the site(s) of variant virus selection within the embryonated egg. In this report we show that both the cells of the chorioallantoic membrane (CAM) and the fluids from embryonated chicken eggs are capable of selecting variant influenza viruses, but that these variants are distinct at the molecular level depending on the conditions of virus propagation. Serial passage of viruses in cells of the chorioallantoic membrane selects one set of variants which possess specific amino acid changes near the receptor binding pocket of the hemagglutinin molecule characteristic of viruses grown in embryonated eggs. However, passage of the same viruses in mammalian tissue culture cells supplemented with egg fluids selects a separate set of hemagglutinin variants also characteristic of viruses grown in eggs, yet at different residues from those observed following passage in CAM. These results suggest that two separate mechanisms may exist in the embryonated egg that lead to the selection of variant influenza viruses: one at the cellular level and another at the extracellular level.

Allantois↗
PubMedDate not supplied

Genetics of house flies. Variability studies with North Dakota, Texas, and Florida populations.

Genetic data were used to compare the structure of native house fly populations collected in North Dakota, Texas, and Florida. Recombination studies with mutant markers on chromosomes 3 and 4 indicated a lack of inversion polymorphism among the three populations in those areas of the genetic map studied. Significant differences were observed among flies from the three regions with regard to the frequency of 1) females that produced only male progeny, and 2) male-determining 3rd chromosomes (IIIm chromosomes). However, the North Dakota and Texas flies were more similar to each other than to the Florida flies since populations from the two former areas possessed a low frequency of both male-producing females and IIIm chromosomes; in contrast, the Florida population was void of females that produced males only and a high percentage if not all Florida males appeared to possess the IIIm male-determining mechanism. Tests for recessive lethal 3rd chromosomes showed that there was no significant difference in the frequency of lethal factors recovered from the North Dakota and Texas flies; the presence of IIIm chromosomes in Florida males precluded the recovery of lethal factors from this population by the method employed. The data suggest that house fly strains to be employed in genetic control programs should 1) originate from target control areas to avoid possible behavioral differences existing among flies from different locales, 2) be initiated with as many flies as possible to provide a background for the maintenance of variability, and 3) be renewed periodically with field-collected material since the genotype may be capable of rapid reorganization in response to laboratory selection pressures.

Animals↗
PubMed1992

Evidence for genetic heterogeneity in hereditary hydronephrosis caused by pelvi-ureteric junction obstruction, with one locus assigned to chromosome 6p.

Hereditary hydronephrosis (MIM 143400) is an autosomal dominant trait that causes unilateral or bilateral pelvi-ureteric junction (PUJ) obstruction. Linkage analysis was undertaken in 5 families with hereditary PUJ obstruction using the major histocompatibility complex locus as a test marker. The data as a whole supported a hereditary hydronephrosis locus on 6p. Maximal lod scores were 3.090 at a recombination fraction of 0.1 with full penetrance, and 2.486 at a recombination fraction of 0.1 with a penetrance of 90%. However, analysis of two point lod scores using the HOMOG program revealed significant evidence for genetic heterogeneity with one locus on 6p in 4 of the families, and a different locus in one family. After exclusion of this unlinked family, two point analysis gave a maximal lod score of 3.9 at a recombination fraction of 0.05 with full penetrance, and 4.2 at a recombination fraction of 0.0 with 90% penetrance. These data support the assignment of one of the loci for hereditary hydronephrosis to chromosome 6p.

Chromosomes, Human, Pair 6↗
PubMed2007

A new model for the population pharmacokinetics of didanosine in healthy subjects.

Didanosine (ddI) is a component of highly active antiretroviral therapy drug combinations, used especially in resource-limited settings and in zidovudine-resistant patients. The population pharmacokinetics of ddI was evaluated in 48 healthy volunteers enrolled in two bioequivalence studies. These data, along with a set of co-variates, were the subject of a nonlinear mixed-effect modeling analysis using the NONMEM program. A two-compartment model with first order absorption (ADVAN3 TRANS3) was fitted to the serum ddI concentration data. Final pharmacokinetic parameters, expressed as functions of the co-variates gender and creatinine clearance (CL CR), were: oral clearance (CL = 55.1 + 240 x CL CR + 16.6 L/h for males and CL = 55.1 + 240 x CL CR for females), central volume (V2 = 9.8 L), intercompartmental clearance (Q = 40.9 L/h), peripheral volume (V3 = 62.7 + 22.9 L for males and V3 = 62.7 L for females), absorption rate constant (Ka = 1.51/h), and dissolution time of the tablet (D = 0.43 h). The intraindividual (residual) variability expressed as coefficient of variation was 13.0%, whereas the interindividual variability of CL, Q, V3, Ka, and D was 20.1, 75.8, 20.6, 18.9, and 38.2%, respectively. The relatively high (>30%) interindividual variability for some of these parameters, observed under the controlled experimental settings of bioequivalence trials in healthy volunteers, may result from genetic variability of the processes involved in ddI absorption and disposition.

Adolescent↗
PubMed2003

QTL and candidate genes phytoene synthase and zeta-carotene desaturase associated with the accumulation of carotenoids in maize.

Carotenoids are a class of fat-soluble antioxidant vitamin compounds present in maize ( Zea mays L.) that may provide health benefits to animals or humans. Four carotenoid compounds are predominant in maize grain: beta-carotene, beta-cryptoxanthin, zeaxanthin, and lutein. Although beta-carotene has the highest pro-vitamin A activity, it is present in a relatively low concentration in maize kernels. We set out to identify quantitative trait loci (QTL) affecting carotenoid accumulation in maize kernels. Two sets of segregating families were evaluated-a set of F2:3 lines derived from a cross of W64a x A632, and their testcross progeny with AE335. Molecular markers were evaluated on the F2:3 lines and a genetic linkage map created. High-performance liquid chromatography was performed to measure beta-carotene, beta-cryptoxanthin, zeaxanthin, and lutein on both sets of materials. Composite interval mapping identified chromosome regions with QTL for one or more individual carotenoids in the per se and testcross progenies. Notably QTL in the per se population map to regions with candidate genes, yellow 1 and viviparous 9, which may be responsible for quantitative variation in carotenoids. The yellow 1 gene maps to chromosome six and is associated with phytoene synthase, the enzyme catalyzing the first dedicated step in the carotenoid biosynthetic pathway. The viviparous 9 gene maps to chromosome seven and is associated with zeta-carotene desaturase, an enzyme catalyzing an early step in the carotenoid biosynthetic pathway. If the QTL identified in this study are confirmed, particularly those associated with candidates genes, they could be used in an efficient marker-assisted selection program to facilitate increasing levels of carotenoids in maize grain.

Alkyl and Aryl Transferases↗
PubMed2026

Unveiling clinical and genetic landscapes of MMA and CBS: insights from whole exome sequencing in a tertiary care setting.

BACKGROUND: MMA and CBS deficiency are rare autosomal recessive metabolic disorders caused by defects in cobalamin metabolism and cystathionine-beta-synthase activity, respectively. Advanced molecular genetic techniques, have become essential for diagnosing these conditions. This study aimed to analyze the genetic variations in three MMA and four CBS deficiency cases using WES and correlate the findings with clinical, biochemical, and treatment outcomes. METHODS: Clinical evaluation, biochemical testing, neuroimaging, and WES were performed. WES data were analyzed using the reference genome GRCh37, and variants were classified according to ACMG guidelines. Treatment outcomes were monitored for three months post-intervention. RESULTS: In MMA cases, a homozygous pathogenic variant (c.394 C > T, p.Arg132Ter) in MMACHC was identified in all three patients. Biochemical abnormalities included methylmalonic aciduria, elevated homocysteine, and megaloblastic anemia. Hydroxycobalamin therapy improved behavioral, cognitive, and dermatological symptoms, though residual neuropathy persisted in one case. In CBS deficiency, pathogenic variants in CBS (c.992 C > T, p.Ala331Val; c.862 G > A, p.Ala288Thr; c.700 G > A, p.Asp234Asn) were identified. Clinical features included developmental delayed milestones, lens dislocation, and vascular complications. Treatment outcomes varied based on early diagnosis and compliance. CONCLUSION: This study highlights the importance of newborn screening program with WES in diagnosing and managing MMA and CBS deficiency, facilitating early intervention, improving clinical outcomes, and supporting precision medicine approaches. IMPACT: Early newborn screening and diagnosis are critical for effective treatment and improved patient outcomes. Novel clinical and pathogenic variants will expand the current understanding of these disorders. WES enhances the diagnostic precision for MMA and CBS deficiency, facilitating timely intervention and superior clinical management. Accurate and early detection of treatable IEMs through NBS can significantly reduce disease burden and healthcare costs.

Child, Preschool↗
PubMed1996

The effects of social structure, geographical structure, and population size on the evolution of mitochondrial DNA: I. A simulation model.

A program simulating the distribution of variation in mitochondrial DNA in macaques is described. Empirical studies of the rates of nucleotide substitution and geographical patterning of mtDNA variation in these and other monkey species have demonstrated striking differences from equivalent measures of nuclear DNA and called into question the assumptions informing the use of mtDNA to elucidate phylogenetic relationships in organisms with relatively complex social organization. The model presented here incorporates social-structural variables as well as geographical structure and population size in order to clarify the determinants of the pattern of mtDNA evolution in macaques. The program, SHINES (Simulation of Hereditary Innovations in Neutral Evolution of Simians), employs an economical procedure for representing the haplotypes of the animals in the simulated population.

Algorithms↗
PubMed1993

Alignment and comparison of multiple related DNA sequences can be improved by consideration of known patterns of mutation.

The rate at which bases are replaced in mammalian DNA is influenced by the sequence involved. I have modified a multiple sequence alignment and comparison program to take account of the observed patterns of base replacement in mammals, and used the program to analyse 100 human Alu sequences. The results show that using a sequence matching matrix based on the actual rate of base replacement, as opposed to arbitrary base matching matrix, gives significant differences in the way that sequences are aligned and compared with each other. Use of the observed matching matrix gives significantly better discrimination between sub-families of Alu sequences than conventional methods, and shows that comparison systems which take account of the mechanism of mutation give more biologically realistic results.

Animals↗
PubMed1986

Between- and within-breed genetic analysis of calving traits and survival to weaning in beef cattle.

Data for gestation length, birth weight, calving difficulty (percent assisted) and survival from birth to weaning were analyzed from 4,639 calves by 290 sires of 14 Bos taurus breeds (Hereford, Angus, Jersey, South Devon, Limousin, Simmental, Charolais, Red Poll, Brown Swiss, Gelbvieh, Maine Anjou, Chianina, Pinzgauer and Tarentaise) mated to Hereford and Angus cows. The calves were produced over a 7-yr period in a germ plasm evaluation program. Variance components were estimated for breed of sire (sigma 2b), sire within breed of sire (sigma 2s) and progeny within sire (sigma 2w) random effects. Estimates of sigma 2b and sigma 2s direct genetic variance were similar for gestation length and calf survival. Estimates of sigma 2b genetic variance were greater than for sigma 2s for birth weight and calving difficulty. Estimates of total heritability [h2t = 4(sigma 2b + sigma 2s)/(4 sigma 2b + sigma 2s + sigma 2w)] and within-breed heritability (h2w = 4 sigma 2s/sigma 2s + sigma 2w) indicated that gestation length (h2t = .77, h2w = 64) and birth weight (h2t = .79, h2w = .46) are under a high degree of direct genetic control, calving difficulty (h2t = .42, h2w = .21) is under a moderate degree of direct genetic control and calf survival (h2t = .11, h2w = .07) is under a low degree of direct genetic control. Estimates of genetic correlation for between (rb) - and within-breed (rg) sources of genetic variation were comparable in direction, but tended to be stronger between than within breeds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Preparing for the future: the status of genetics education in diploma-level training courses for nurses in the UK.

This paper offers new information about genetics education provided by diploma level training programmes for nurses in the UK. Those responsible for the development and provision of curricula were asked to complete a questionnaire that attempted to assess the nature of genetics education and their attitudes towards it. The response rate was 84%. Whist genetics teaching is included on all but two training courses, variation in content, delivery and timetable allocation indicates disparity. Genetics is taught for 10 hours or less on most courses, utilizing a limited number of approaches. Most courses do not have compulsory assessment. The majority of respondents (81%) agreed that genetics will have a major impact on health care, and will become an increasingly important issue in education. A small majority (58%) agreed that genetics should have a higher profile in professional training yet many respondents (68%) felt that the teaching they were already offering was appropriate to meet patients' needs. In the absence of any clear national framework for delivery and assessment of genetics education, the author questions whether current training is sufficient to provide nurses with the basic genetic literacy needed to respond to developments in genetics as they impact on health care.

Clinical Competence↗