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PubMed1986

Quantitative computer analysis of signal sequence homologies in DNA.

Homologies to prokaryotic recognition sites for RNA polymerase, ribosomes, and cyclic-AMP receptor protein (CRP), are analyzed by a new computer program using weighting factors to account for the statistical variation at each position of the consensus. Known signal sequence sites are easily detected by this algorithm, and other sites with equally strong homology are found whose biological function is still unknown. Some sites are biologically active even though they have very weak homology. No arbitrary 'cutoff score' can distinguish active recognition sites from inactive homologies; experiments must determine why certain weak homologies are able to function while others are not.

Algorithms↗

PubMed1997

Comprehensive, rapid and sensitive detection of sequence variants of human mitochondrial tRNA genes.

In the present study, a comprehensive, rapid and sensitive method for screening sequence variation of the human mitochondrial tRNA genes has been developed. For this purpose, the denaturing gradient gel electrophoresis (DGGE) technique has been appropriately modified for simultaneous mutation analysis of a large number of samples and adapted so as to circumvent the problems caused by the anomalous electrophoretic behavior of DNA fragments encoding tRNA genes. Eighteen segments of mitochondrial DNA (mtDNA), each containing a single uniform melting domain, were selected to cover all tRNA-encoding regions using the computer program MELT94. All 18 segments were simultaneously analyzed by electrophoresis through a single broad range denaturing gradient gel under rigorously defined conditions, which prevent band broadening and other migration abnormalities from interfering with detection of sequence variants. All base substitutions tested, which include six natural mutations and 14 artificially introduced ones, have been detected successfully in the present study. Several types of evidence strongly suggest that the anomalous behavior in DGGE of tRNA gene-containing mtDNA fragments reflects their tendency to form temporary or stable alternative secondary structures under semi-denaturing conditions. The high sensitivity of the method, which can detect as low as 10% of mutant mtDNA visually, makes it valuable for the analysis of heteroplasmic mutations.

Cell Line↗

PubMed2005

Molecular marker-based genetic diversity assessment of Striga-resistant maize inbred lines.

Striga-resistant maize inbred lines are of interest to maize breeding programs in the savannas of Africa where the parasitic weed is endemic and causes severe yield losses in tropical maize. Assessment of the genetic diversity of such inbred lines is useful for their systematic and efficient use in a breeding program. Diversity analysis of 41 Striga-resistant maize inbred lines was conducted using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers to examine the genetic relationships among these lines and to determine the level of genetic diversity that exists within and between their source populations. The two marker systems generated 262 and 101 polymorphic fragments, respectively. Genetic similarity (GS) values among all possible pairs of inbred lines varied from 0.45 to 0.95, with a mean of 0.61+/-0.002 for AFLPs, and from 0.21 to 0.92, with a mean of 0.48+/-0.003, for SSRs. The inbred lines from each source population exhibited a broad range of GS values with the two types of markers. Both AFLPs and SSRs revealed similar levels of within population genetic variation for all source populations. Cluster and principal component analysis of GS estimates with the two markers revealed clear differentiation of the Striga-resistant inbred lines into groups according to their source populations. There was clear separation between early- and late-maturing Striga-resistant inbred lines. Considering the paucity of germplasm with good levels of resistance to Striga in maize, the broad genetic diversity detected within and among source populations demonstrates the genetic potential that exists to improve maize for resistance to Striga.

Breeding↗

PubMed1999

Retinoids and mammalian development.

All vertebrate embryos require retinoic acid (RA) for fulfilment of the developmental program encoded in the genome. In mammals, maternal homeostatic mechanisms minimize variation of retinoid levels reaching the embryo. Retinol is transported as a complex with retinol-binding protein (RBP): transplacental transfer of retinol and its uptake by the embryonic tissues involves binding to an RBP receptor at the cell surface. Embryonic tissues in which this receptor is present also contain the retinol-binding protein CRBP I and the enzymes involved in RA synthesis; the same tissues are particularly vulnerable to vitamin A deficiency. In the nucleus, the RA signal is transduced by binding to a heterodimeric pair of retinoid receptors (RAR/RXR). In general, the receptors show functional plasticity, disruption of one RAR or RXR gene having minor or no effects on embryogenesis. However, genetic studies indicate that RXR alpha is essential for normal development of the heart and eye. Excess RA causes abnormalities of many systems; altered susceptibility to RA excess in mice lacking RAR gamma or RXR alpha suggests that the teratogenic signal is transduced through different receptors compared with physiological RA function in the same tissue.

Animals↗

PubMed2002

Polygenic susceptibility to breast cancer and implications for prevention.

The knowledge of human genetic variation that will come from the human genome sequence makes feasible a polygenic approach to disease prevention, in which it will be possible to identify individuals as susceptible by their genotype profile and to prevent disease by targeting interventions to those at risk. There is doubt, however, regarding the magnitude of these genetic effects and thus the potential to apply them to either individuals or populations. We have therefore examined the potential for prediction of risk based on common genetic variation using data from a population-based series of individuals with breast cancer. The data are compatible with a log-normal distribution of genetic risk in the population that is sufficiently wide to provide useful discrimination of high- and low-risk groups. Assuming all of the susceptibility genes could be identified, the half of the population at highest risk would account for 88% of all affected individuals. By contrast, if currently identified risk factors for breast cancer were used to stratify the population, the half of the population at highest risk would account for only 62% of all cases. These results suggest that the construction and use of genetic-risk profiles may provide significant improvements in the efficacy of population-based programs of intervention for cancers and other diseases.

Breast Neoplasms↗

PubMed2026

Dissecting the genetics of forage quality traits in soft red winter wheat in the U.S. southeast region.

Winter wheat plays a viable role in agriculture, not only as a primary grain crop but also as a valuable forage source that bridges fall-spring forage gaps in many regions, including the southeastern (SE) U.S. Despite its nutritive potential, genetic basis of forage-quality traits remains insufficiently understood, limiting breeding efforts for dual-purpose cultivars. This study aimed to dissect the genetic architecture of forage quality in 182 soft red winter wheat (SRWW) genotypes adapted to the SE U.S. using genome-wide association study (GWAS). Field experiments were carried out in randomized complete block design across three Georgia locations over two growing seasons (2023-2025), with forage sampled at the end of tillering and evaluated using near-infrared reflectance spectroscopy. Significant phenotypic variation was observed for dry matter (DM), crude protein (CP), acid and neutral detergent fiber (ADF, NDF), acid detergent lignin (ADL), total digestible nutrients (TDN), sugars (SUG), and relative forage quality (RFQ). Heritability estimates ranged from low-to-moderate in combined environments and from low-to-high within individual locations. Correlation analysis revealed strong positive associations among fiber-related traits and negative associations with TDN, RFQ, and SUG, while CP declined with increasing fiber. Genome-wide association analysis identified 282 significant marker-trait associations (P < 1×10-4) across 19 chromosomes, which were consolidated into 121 QTLs, including 27 major-effect QTLs. Three QTLs QRfq.uga-3B.1, QRfq.uga-3B.2 (RFQ) and QDm/Sug.uga-7A (DM, SUG) were stable across locations while QAdf/Adl.uga-2A (ADF, ADL) and QDm/Sug.uga-7A (DM, SUG) indicated multi-trait control. Notably, 25 of the 27 major QTLs were putatively novel, highlighting substantial untapped allelic diversity for forage-quality improvement in SE SRWW. Favorable allele accumulation resulted in an overall improvement in forage quality, increasing desirable nutritive traits (DM, RFQ, SUG, CP) while reducing undesirable traits (ADF, ADL). Candidate gene analysis linked six major QTLs with genes implicated in abiotic stress response, plant development, and metabolic regulation, supporting their functional relevance in forage-quality determination. Incorporating these loci into breeding programs provides a robust genetic framework for marker-assisted selection, enabling the development of dual-purpose wheat cultivars with enhanced forage quality, thereby strengthening wheat's utility as a reliable forage resource during periods of seasonal feed scarcity in SE production systems.

GWAS↗

PubMed2026

DNA Methylation Profiling of Pediatric Ectomesenchymoma Supports Embryonal Rhabdomyosarcoma-Like Epigenetic Identity.

Ectomesenchymoma is a rare, biphenotypic pediatric tumor combining rhabdomyoblastic and neuroectodermal differentiation. We characterize two novel cases through integrated genomics and the first report of genome-wide DNA methylation profiling. Both tumors harbored RAS-pathway mutations (HRAS p.Gly13Arg; NRAS p.Gln61His). Methylation analysis, including microdissected components, consistently aligned ectomesenchymoma with the embryonal rhabdomyosarcoma superfamily, revealing a shared myogenic epigenetic program despite neural differentiation. Shared copy-number profiles across distinct histological regions supported a monoclonal origin. Overall, our data support a close biological relationship between ectomesenchymoma and embryonal rhabdomyosarcoma and indicate that RAS-pathway testing and methylation profiling can significantly refine diagnostic precision.

Humans↗

PubMed2003

A parallel optimization approach for controlling allele diversity in conservation schemes.

We propose a novel method to control allelic diversity in conservation schemes based on an optimization problem, characterized by a convex program subject to integer linear constraints. Departing from previous studies considering similar problems, we implement a parallel simulated annealing algorithm to minimize the number of alleles lost across generations. The proposed algorithm shows excellent timing and minimization performances. Execution time decreases linearly with the number of processors used, providing similar results in all cases.

Algorithms↗

PubMed1999

Partial nucleotide sequencing and molecular evolution of epidemic causing Dengue 2 strains.

To study the genetic variability and to detect evolutionary changes and movement of dengue 2 (DEN-2) strains, nucleotide sequencing of the envelope protein gene and the nonstructural protein 1 gene junction was performed for 9 isolates from the 1996 Delhi epidemic and 1 isolate from the 1967 Delhi epidemic. The epidemic strains had a divergence of 10%-11% from the 1967 strains, but were quite similar to DEN-2 isolates from Seychelles, Somalia, and Torres Strait. In addition, the sequence data were compared to the prototype DEN-2 strain, New Guinea C, and other published DEN-2 sequences from different parts of the world. The phylogenetic analysis by the Molecular Evolutionary Genetics Analysis program suggests that the 1996 Delhi isolates of DEN-2 were genotype IV. The 1967 isolate was similar to a 1957 isolate of DEN-2, P9-122, from India, and was classified as genotype V. This study indicates that earlier DEN-2 strains of genotype V have been replaced by genotype IV.

Base Sequence↗

PubMed2006

ModelTest Server: a web-based tool for the statistical selection of models of nucleotide substitution online.

ModelTest server is a web-based application for the selection of models of nucleotide substitution using the program ModelTest. The server takes as input a text file with likelihood scores for the set of candidate models. Models can be selected with hierarchical likelihood ratio tests, or with the Akaike or Bayesian information criteria. The output includes several statistics for the assessment of model selection uncertainty, for model averaging or to estimate the relative importance of model parameters. The server can be accessed at http://darwin.uvigo.es/software/modeltest_server.html.

Base Composition↗

PubMed2004

Stability of genetic evaluations for active artificial insemination bulls.

Genetic evaluations for milk, fat, and protein from 1995 through August 2003 for 17,987 Holstein bulls in active artificial insemination (AI) service were examined for changes to the November 2003 evaluation. Evaluations for active AI bulls at each of 31 evaluation dates showed mean declines to November 2003. No evidence was seen of a worsening situation over time. Bulls' early evaluations with active AI status showed much larger declines, but this overevaluation diminished and essentially disappeared after 3 yr. The bulls with first active AI evaluations since 1995 were the primary focus of the study. The influx of second-crop daughters did not appear to cause a decline in evaluations for these bulls, attesting to the successful modification to the genetic evaluation system by expanding the genetic variance of short records. Mean declines and the variation of those differences were generally similar by bull sampling organization. A change from active to inactive AI status was generally concurrent with a decline in predicted transmitting ability (PTA). Bulls coded as having standard AI sampling declined less than bulls coded as having other sampling, but the differences were much less than in previous reports. Larger increases in reliability were generally associated with greater declines in PTA, and the magnitude of these changes decreased over time (increasing evaluation number). Change in reliability underpredicted the variance of change in PTA, indicating that other important factors contribute or that the assumptions for the calculation of the expected change in PTA are not met. Declines in estimated merit over time are not sufficient to alter present genetic selection programs, but reasons for the declines continue to elude explanation.

Animals↗

PubMed2002

Mapping quantitative trait loci for plant height in wheat (Triticum aestivum L.) using a F2:3 population.

To detect quantitative trait loci (QTLs) controlling plant height, the plant height of 240 F2:3 lines derived from the cross of a dwarf wheat line ND3338 with a tall line F390, was assessed in field trials at two locations with three replications in 2000 and 2001. Microsatellite markers were used to construct a framework linkage map containing 215 loci with 21 linkage groups, and covering the whole genome about 3600cM. With the method of interval mapping, seven putative QTLs affecting plant height were detected on chromosomes 1B, 4B (two regions), 6A (two regions), 6D and 7A, respectively. Phenotypic variations explained by each QTL ranged from 5.2% to 50.1%, and in each environment the total putative QTLs explained about 64.8%-75% of the total phenotypic variation respectively. A major QTL located on chromosome arm 4BS near the locus Xgwm113, around the Rht-Blb locus, explained a large part of the phenotypic variation (27.8%-36.2% depending on the years or the locations). Except the QTL on chromosome 7A, all the other QTLs from ND3338 decreased the plant height, variously from 0.94 cm to 9.33 cm. Most of the identified QTLs were consistent in all the environments, and should be useful in future marker-assisted-selection programs for breeding dwarf and semi-dwarf wheat cultivars.

Chromosome Mapping↗

PubMed2006

QualitySNP: a pipeline for detecting single nucleotide polymorphisms and insertions/deletions in EST data from diploid and polyploid species.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are important tools in studying complex genetic traits and genome evolution. Computational strategies for SNP discovery make use of the large number of sequences present in public databases (in most cases as expressed sequence tags (ESTs)) and are considered to be faster and more cost-effective than experimental procedures. A major challenge in computational SNP discovery is distinguishing allelic variation from sequence variation between paralogous sequences, in addition to recognizing sequencing errors. For the majority of the public EST sequences, trace or quality files are lacking which makes detection of reliable SNPs even more difficult because it has to rely on sequence comparisons only. RESULTS: We have developed a new algorithm to detect reliable SNPs and insertions/deletions (indels) in EST data, both with and without quality files. Implemented in a pipeline called QualitySNP, it uses three filters for the identification of reliable SNPs. Filter 1 screens for all potential SNPs and identifies variation between or within genotypes. Filter 2 is the core filter that uses a haplotype-based strategy to detect reliable SNPs. Clusters with potential paralogs as well as false SNPs caused by sequencing errors are identified. Filter 3 screens SNPs by calculating a confidence score, based upon sequence redundancy and quality. Non-synonymous SNPs are subsequently identified by detecting open reading frames of consensus sequences (contigs) with SNPs. The pipeline includes a data storage and retrieval system for haplotypes, SNPs and alignments. QualitySNP's versatility is demonstrated by the identification of SNPs in EST datasets from potato, chicken and humans. CONCLUSION: QualitySNP is an efficient tool for SNP detection, storage and retrieval in diploid as well as polyploid species. It is available for running on Linux or UNIX systems. The program, test data, and user manual are available at http://www.bioinformatics.nl/tools/snpweb/ and as Additional files.

Base Sequence↗

PubMed2001

Problems in the definition, interpretation, and evaluation of genetic heterogeneity.

Suppose that we wish to classify families with multiple cases of disease into one of three categories: those that segregate mutations of a gene of interest, those which segregate mutations of other genes, and those whose disease is due to nonhereditary factors or chance. Among families in the first two categories (the hereditary families), we wish to estimate the proportion, p, of families that segregate mutations of the gene of interest. Although this proportion is a commonly accepted concept, it is well defined only with an unambiguous definition of "family." Even then, extraneous factors such as family sizes and structures can cause p to vary across different populations and, within a population, to be estimated differently by different studies. Restrictive assumptions about the disease are needed, in order to avoid this undesirable variation. The assumptions require that mutations of all disease-causing genes (i) have no effect on family size, (ii) have very low frequencies, and (iii) have penetrances that satisfy certain constraints. Despite the unverifiability of these assumptions, linkage studies often invoke them to estimate p, using the admixture likelihood introduced by Smith and discussed by Ott. We argue against this common practice, because (1) it also requires the stronger assumption of equal penetrances for all etiologically relevant genes; (2) even if all assumptions are met, estimates of p are sensitive to misspecification of the unknown phenocopy rate; (3) even if all the necessary assumptions are met and the phenocopy rate is correctly specified, estimates of p that are obtained by linkage programs such as HOMOG and GENEHUNTER are based on the wrong likelihood and therefore are biased in the presence of phenocopies. We show how to correct these estimates; but, nevertheless, we do not recommend the use of parametric heterogeneity models in linkage analysis, even merely as a tool for increasing the statistical power to detect linkage. This is because the assumptions required by these models cannot be verified, and their violation could actually decrease power. Instead, we suggest that estimation of p be postponed until the relevant genes have been identified. Then their frequencies and penetrances can be estimated on the basis of population-based samples and can be used to obtain more-robust estimates of p for specific populations.

Family Health↗

PubMed2006

Genetic diversity of sorghum accessions resistant to greenbugs as assessed with AFLP markers.

Sorghum, Sorghum bicolor (L.) Moench, is the fifth most important cereal crop grown worldwide and the fourth in the United States. Greenbug, Schizaphis graminum (Rondani), is a major insect pest of sorghum with several biotypes reported to date. Greenbug biotype I is currently the most prevalent and most virulent on sorghum plants. Breeding for resistance is an effective way to control greenbug damage. A successful breeding program relies in part upon a clear understanding of breeding materials. However, the genetic diversity and relatedness among the greenbug biotype I resistant accessions collected from different geographic origins have not been well characterized, although a rich germplasm collection is available. In this study, 26 sorghum accessions from 12 countries were evaluated for both resistance to greenbug biotype I and genetic diversity using fluorescence-labeled amplified fragment length polymorphism (AFLP). Twenty-six AFLP primer combinations produced 819 polymorphic fragments indicating a relatively high level of polymorphism among the accessions. Genetic similarity coefficients among the sorghum accessions ranged from 0.69 to 0.90. Cluster analysis indicated that there were two major groups based on polymorphic bands. This study has led to the identification of new genetic sources of sorghum with substantial genetic variation and distinct groupings of resistant accessions that have the potential for use in the development of durable greenbug resistant sorghum.

Animals↗

PubMed2006

Sensitivity to IGF-I in short children born small for gestational age.

About 5% of newborns are classified as small for gestational age (SGA) and of these, 10-15% do not catch up in growth by 2 yr of age. In addition to genetic mutations in the GH-IGF-IGFBP axis, environmental factors may re-program growth during fetal development leading to altered hormone sensitivity. This review summarizes the importance of GH treatment in SGA children. Although GH dose is the most relevant factor for growth response in children born SGA, higher GH doses are needed in SGA subjects to induce a growth response comparable to GH deficient (GHD) patients. Therapeutic difficulties possibly arise from the impaired hormone sensitivity along the GH-IGF-IGFBP axis. Indeed, several observations point towards impaired sensitivity to hormones involved in the GH-IGF-IGFBP axis in children born SGA. The inability to classify SGA patients according to the relative GH and IGF-I concentrations is probably due to the large variation in hormone sensitivity patterns in patients with SGA. Simple laboratory tests need to be established that directly quantify sensitivity to parameters in the GH-IGF-IGFBP axis, such as IGF-I. Adequate additional therapies could in future result in positive effects on co-morbidities associated with IGF-I insensitivity in SGA children in addition to height gain.

Body Height↗

PubMed2006

Analysis of dental anomalies in the Siberian mole, Talpa altaica (Insectivora, Talpidae).

We re-examined tooth variation in specimens of the Siberian mole, Talpa altaica, from the collection of the Siberian Zoological Museum and discuss the mechanisms of dental evolution. The number of teeth counted in 1789 specimens ranged from 34 to 47, and supernumerary, absent, and connate teeth were observed. The most frequent tooth anomaly was an absent tooth in the premolar region (200 maxillary first premolars and 190 mandibular third premolars), which does not support Fujita and Kirino's terminal reduction hypothesis in the mandible [Fujita T, Kirino T. Ha No Kaibougaku. 21st ed. Tokyo: Kanehara Publishers Inc.; 1976 (in Japanese)]. Supernumerary teeth were found in premolar rows and in the incisor and molar regions. An maxillary fourth molar, positioned distal to the normal third molar, was thought to result from a genetically programmed atavistic event during the natal stages. Connate teeth were observed only in the premolar rows and were thought to have developed with the fusion of two independent tooth germs. Connate premolars appeared to result from an expression of an incomplete division of tooth germ at an early developmental stage or a reunion of independent tooth germs, based on the morphological similarity of the normal and supernumerary premolars. These extraordinarily frequent tooth anomalies of T. altaica are of much interest both in terms of tooth development and classification.

Animals↗

PubMed1992

Analysis of algebraic weighted least-squares estimators for enzyme parameters.

An algorithm for the least-squares estimation of enzyme parameters Km and Vmax. is proposed and its performance analysed. The problem is non-linear, but the algorithm is algebraic and does not require initial parameter estimates. On a spreadsheet program such as MINITAB, it may be coded in as few as ten instructions. The algorithm derives an intermediate estimate of Km and Vmax. appropriate to data with a constant coefficient of variation and then applies a single reweighting. Its performance using simulated data with a variety of error structures is compared with that of the classical reciprocal transforms and to both appropriately and inappropriately weighted direct least-squares estimators. Three approaches to estimating the standard errors of the parameter estimates are discussed, and one suitable for spreadsheet implementation is illustrated.

Algorithms↗