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At least 1,081 records · Page 60Linked to original sources
PubMed1998

Genetic variation of mitochondrial cytochrome b genes among the subspecies of koala, Phascolarctos cinereus.

A conserved DNA region among the subspecies of koala, of mitochondrial cytochrome b gene, was employed to analyze the genetic variation among 3 available subspecies of koala. This conserved sequence, 307 bp DNA, was sequenced using polymerase chain reaction and direct DNA sequencing technique. Substitutions in the nucleotide sequences were observed, with which koalas can be divided into 3 DNA haplotypes subspecies, but the molecular data provided inconsistency with current classification of the 3 subspecies of koala.

Amino Acid Sequence↗
PubMedDate not supplied

Developmental and genetic disorders in spermatogenesis.

The most common cause of male infertility is idiopathic. Fresh insights based on genetic and molecular analysis of the human genome permit classification of formerly unexplained disorders in spermatogenesis. In this article, we review new procedures that expand diagnostic and therapeutic approaches to male infertility. Recombinant DNA technology makes it possible to detect specific chromosomal and/or genetic defects among infertile patients. The identification of genes linked to disorders in spermatogenesis and male sexual differentiation has increased exponentially in the past decade. Genetic defects leading to male factor infertility can now be explained at the molecular level, even though the germ cell profile of infertile patients is too variable to permit classification of the clinical phenotype. Increasing knowledge of genes that direct spermatogenesis provides important new information about the molecular and cellular events involved in human spermatogenesis. Molecular analysis of chromosomes and/or genes of infertile patients offers unique opportunities to uncover the aetiology of genetic disorders in spermatogenesis. Increasing numbers of cases, previously classified as idiopathic, can now be diagnosed to facilitate the treatment of infertile men. Advanced knowledge also poses ethical dilemmas, since children conceived with assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) are at risk for congenital abnormalities, unbalanced complements of chromosomes and male infertility.

Chromosome Aberrations↗
PubMed1996

The epidemiology of Hodgkin's disease.

Much of the epidemiological heterogeneity of HD incidence reflects the behaviour of the NS subtype, at least in the USA. Incidence variation across races (except Asians) and time periods is most marked in this subtype. In young adults with HD, there is compelling evidence for social class modification of risk consistent with an infectious aetiology; limited data suggest that this effect occurs within the NS subtype, but considerable evidence indicates that it does not primarily involve EBV infection. Findings from familial aggregation studies and HLA associations point to inherited susceptibility to this subtype. Despite little sex difference for NS in young adulthood in the latest incidence data, parity nevertheless appears to be protective against this subtype for women. Therefore, the greater increase for females than males in the incidence of young-adult NS in recent years may reflect the impact of population trends towards later childbearing and lower parity. This change, as well as the concomitant smaller family sizes and growing affluence, could explain part of the burgeoning incidence of NS in young adults in the USA. These observations suggest that NS in young adults constitutes a separate disease, probably of infectious origin. The incongruous occurrence of this subtype in older adults, and the presence of EBV in some NS cases, could reflect heterogeneity within NS, for example, representing features of the cellular phase of NS (Cozen et al, 1992; Medeiros and Greiner, 1995). For the non-NS subtypes, many of the factors that predict risk of NS may also be relevant. Patterns of social class determinants in children and older adults, the age groups at risk for MC, support involvement of an infectious precursor given intense exposure, and EBV is a likely candidate, based on its high prevalence in these groups. However, little aetiological research has been directed explicitly at the non-NS subtypes. Considerable effort has gone into exploring an infectious aetiology of HD. Recently, this line of investigation has moved beyond social class determinants to molecular epidemiological studies of EBV and, to a lesser degree, other potentially involved viruses. The roles of genetic susceptibility and sex hormones also represent promising areas for exploration, particularly in their possible interaction with infectious agents and other environmental factors. Ultimately, clearer epidemiological understanding of HD will be aided by more precise classification of this disease at the molecular level.

Adult↗
PubMed2006

Knowledge-based design of target-focused libraries using protein-ligand interaction constraints.

Here we present a new strategy for designing and filtering potentially massive combinatorial libraries using structural information of a binding site. We have developed a variation of the structural interaction fingerprint (SIFt) named r-SIFt, which incorporates the binding interactions of variable fragments in a combinatorial library. This method takes into account the 3D structure of the active site of the target molecule and translates desirable ligand-target binding interactions into library filtering constraints. We show using the MAP kinase p38 as a test case that we can efficiently analyze and classify compounds on the basis of their abilities to interact with the target in the desired binding mode. On the basis of these classifications, decision tree models were generated using the molecular descriptors of the compounds as predictor variables. Our results suggest that r-SIFt coupled with the classification models should be a valuable tool for structure-based focusing of combinatorial chemical libraries.

Binding Sites↗
PubMed2003

Epithelial and soft tissue tumors of the tracheobronchial tree.

This article provides a broad overview of tumors that can involve the tracheobronchial tree. For the most part, the clinical, radiographic, and endoscopic presentation of these rare tumors does not differ significantly from the more common tumors of the lung. Appropriate classification of many tracheobronchial tumors ultimately requires complete sampling and a thorough microscopic evaluation. The introduction of ancillary diagnostic techniques such as immunohistochemistry and molecular analysis will continue to refine tumor classification.

Adenoma↗
PubMedDate not supplied

Molecular similarity analysis and virtual screening by mapping of consensus positions in binary-transformed chemical descriptor spaces with variable dimensionality.

A novel compound classification algorithm is described that operates in binary molecular descriptor spaces and groups active compounds together in a computationally highly efficient manner. The method involves the transformation of continuous descriptor value ranges into a binary format, subsequent definition of simplified descriptor spaces, identification of consensus positions of specific compound sets in these spaces, and iterative adjustments of the dimensionality of the descriptor spaces in order to discriminate compounds sharing similar activity from others. We term this approach Dynamic Mapping of Consensus positions (DMC) because the definition of reference spaces is tuned toward specific compound classes and their dimensionality is increased as the analysis proceeds. When applied to virtual screening, sets of bait compounds are added to a large screening database to identify hidden active molecules. In these calculations, molecules that map to consensus positions after elimination of most of the database compounds are considered hit candidates. In a benchmark study on five biological activity classes, hits for randomly assembled sets of bait molecules were correctly identified in 95% of virtual screening calculations in a source database containing more than 1.3 million molecules, thus providing a measure of the sensitivity of the DMC technique.

Journal Article↗
PubMed1997

Pathological diagnostic criteria for dementia associated with cortical Lewy bodies: review and proposal for a descriptive approach.

In recent years dementia histologically characterised by the presence of cortical Lewy bodies has been increasingly recognised. There is now need for a scheme for an internationally acceptable scheme for pathological diagnosis and classification so that clinical, pathological and molecular features of disease can be correlated. Recent observations made by different groups in large patient series have used slightly different pathological criteria resulting in at least seven different diagnostic terms. In some patients the only cortical pathology is the presence of Lewy bodies, while in the majority of patients there are coexisting pathological changes which either overlap with those seen in Alzheimer's disease (AD). Cortical Lewy bodies can also be present in patients who do not have any obvious cognitive abnormality. A problem with equating studies from different groups is that different criteria have been used to define AD, so that establishing the relevance of cortical Lewy bodies themselves to cognitive decline and separating this from the contribution which may be related to the AD pathology is problematic. The lesions which appear to be of most relevance to potential cognitive decline in DLB are cortical Lewy bodies, Lewy-related neurites, senile plaques, neurofibrillary tangles, neuronal and synaptic loss, spongiform change, and cortical cholinergic deficits. It is possible to operationally classify patients with cognitive decline and cortical Lewy bodies into three main groups, Cortical Lewy body disease, Cortical Lewy body disease with plaques, and Cortical Lewy body disease with plaques and tangles. There are frequent cases which overlap these groups making operational classification difficult in practice. A descriptive classification, in which the severity of different pathological changes is rated, is easy to use in practice. As new molecular risk factors for AD or DLB are revealed they will need to be related to morphological and clinical features. A descriptive diagnostic assessment for DLB will facilitate such studies and makes no judgements as to what these relationships will be.

Aged↗
PubMed2026

A module-based approach for post-omics, post-GWAS network-based gene classification.

MOTIVATION: Complex traits and diseases are highly polygenic and understanding the full set of genes involved is a central challenge in biomedicine. However, due to sample size limitations and noise (technical and biological), experimental approaches for disease-gene discovery such as transcriptomics and GWAS result in long, noisy, heterogeneous gene lists, which may be trimmed to a subset of likely relevant genes while leaving several false negatives. Computational gene classification approaches, especially those using genome-scale molecular interaction networks, are promising avenues for complementing such experimental findings by analytically expanding observed gene lists based on the functional relatedness between genes. We previously introduced the network-based gene classification approach, GenePlexus, which was rigorously benchmarked to show state-of-the-art performance, especially for predicting novel genes associated with biological processes and fine-grained phenotypes. Network-based gene classification performance,however, declines for diseases, especially when the inputs are omics and GWAS-based long gene lists. RESULTS: Here, we show that these disease gene lists span multiple biological processes spread across the molecular network, and we propose ModGenePlexus, a new network-based gene classification method that takes a two-stage approach. First, clustering and semi-supervised learning decomposes the input gene list into coherent, denoised network gene modules. Then, ModGenePlexus trains supervised (GenePlexus) classifiers for each module and aggregates predictions to return genome-wide rankings. We benchmarked ModGenePlexus across simulated data, transcriptomic signatures, and GWAS datasets (together spanning hundreds of diseases), showing improved recovery of known disease genes compared to GenePlexus. Beyond improved classification, the results of enrichment analysis of ModGenePlexus outputs are much more interpretable by virtue of revealing nuanced biological processes. Together, these results establish ModGenePlexus as a scalable, interpretable tool for gene classification of GWAS- and omics-derived gene lists across diverse biological contexts. AVAILABILITY AND IMPLEMENTATION: ModGenePlexus is freely available on GitHub at https://github.com/krishnanlab/ModGenePlexus, and the full source code and results supporting this study are available on Zenodo at https://zenodo.org/records/19857910.

Genome-Wide Association Study↗
PubMed2000

Molecular genetics of peroxisomal disorders.

Twenty five human peroxisomal disorders have been defined at this time. They are subdivided into two major categories: 1) the disorders of peroxisome biogenesis, in which the organelle fails to form normally, and there are defects that involve multiple peroxisomal functions; and 2) disorders that affect single peroxisomal enzymes. During the last five years the molecular defects have been identified in nearly all. These recent advances have several important implications. They have facilitated diagnosis of affected patients. The improved capacity to provide prenatal diagnosis and heterozygote identification has been of great value for genetic counseling and disease prevention. Study of genotype-phenotype correlations has led to a new and more rational classification system. The identification of the molecular defects and the development of animal models have increased understanding of pathogenetic mechanisms, and have led to novel therapeutic approaches.

Adrenoleukodystrophy↗
PubMed2001

[Genetics of renal tumors].

The quintessence of malignant transformation is the genetic alteration of the tumor progenitor cell, i.e. somatic mutation. The genetic change appearing at chromosome and/or gene level results in the disturbance of the balance of cell proliferation and differentiation. In solid tumors, including renal tumors, the basic genetic mechanism proved to be the loss of function of a specific gene pair caused by loss of the particular chromosome or chromosomal region (monosomy, deletion) or by mutation of the gene. In the well studied Wilms' tumor-aniridia-syndrome the distal part of 11p13 region is deleted. The responsible gene is the WT-1 tumor suppressor gene, a Zn finger type transcription factor. In the majority of cases the mutation of this gene leads to the tumor formation without cytogenetically detectable deletion. For manifestation of the tumor the functional damage of both alleles is needed. In other histological types of renal tumors a great variation of chromosome losses and gains, as well as translocations can be identified. In Wilms tumor of embryonic origin, tumor suppressor genes located on the short arms of chromosomes 16 and 17 play a role in the pathogenesis. Besides, the significance of abnormal genomic imprinting of IGF2 and H19 genes located on 11p15 has also been confirmed. If a part of the embryonic cells do not regress, they may develop to papillary carcinoma together with the appearance of trisomies of chromosomes 7 and 17 and loss of Y. In the transformation process from papillary adenoma to carcinoma, duplication of several chromosomal regions is involved (3q+, +8, +12, +16, +20). The origin of renal carcinoma developing from normal nephron cells is associated with a deletion of 3p and 5q+, while during the progression of the disease further variable chromosome losses appear (6q-, 8p-, 14q-, -9). Tumor-specific cytogenetic and molecular genetic changes confirm the morphological classification of epithelial renal tumors pointing at the relation of the various entities or their independence. Based on cytogenetic alterations, a sequential predictive model of renal tumors can be developed. Individual types, together with joining and sequential appearance of aberrations are in line with the multistep mechanism of carcinogenesis. At the same time, the specific cytogenetic and molecular genetic changes confirm the diagnosis, provide further information about the histological type and progression of the disease. In hereditary cases, the members of the family at risk can be identified by recognizing the possibly associating clinical symptoms and/or by detecting the constitutional mutation of the gene using molecular genetic methods. Consequently, the genetic study of renal tumors plays important role not only in diagnosis and choosing adequate therapy but also in prevention of the disease.

Adenoma↗
PubMed2006

Structure, function and regulation of carboxylesterases.

This review covers current developments in molecular-based studies of the structure and function of carboxylesterases. To allay the confusion of the classic classification of carboxylesterase isozymes, we have proposed a novel nomenclature and classification of mammalian carboxylesterases on the basis of molecular properties. In addition, mechanisms of regulation of gene expression of carboxylesterases by xenobiotics and involvement of carboxylesterase in drug metabolism and enzyme induction are also described.

Amino Acid Sequence↗
PubMed2004

The impact of the completed human genome sequence on the development of novel therapeutics for human disease.

With the official completion of the Human Genome Project in April 2003, we have both the opportunity and the imperative to translate this unprecedented scientific accomplishment into tangible improvements in human health. Medical benefits from the genome will come in stages and can be conceptualized as occurring in three areas: improved understanding of disease causation at the molecular level, improved diagnosis and disease classification based on genetic profiles, and new therapeutics based on targets identified in the genome. These improvements will require increased physician understanding of genetic principles applied to common diseases.

Disease↗
PubMed2001

Glioblastomas with an oligodendroglial component: a pathological and molecular study.

Glioblastoma (GBM) is considered by the WHO classification to represent the most malignant grade of the astrocytic tumors. However, a subset of GBM includes recognizable areas with oligodendroglial features, suggesting that some GBM may also have an oligodendroglial origin. The aim of this study was to analyze the molecular profile of GBM associated with an oligodendroglial component (GBMO). We analyzed a series of 25 GBMO. Loss of heterozygosity (LOH) on 1p and 19q, known as common markers of oligodendroglial tumors, were observed in 40% and 60% of cases, respectively; 72% of the tumors displayed one or both of these markers. All but 4 tumors (84%) showed alterations known to be preferentially involved in the progression of astrocytic tumors to GBM, such as EGFR amplification (44%), P16 deletion (48%), LOH on 10q (64%), PTEN (20%), and TP53 (24%) mutations. Therefore, GBMO displayed all the genetic aberrations found in "standard" GBM with a comparable incidence, but differed from GBM by having a higher rate of LOH on 1p and 19q. These results suggest that GBMO might represent a subgroup of tumors of oligodendroglial origin that is distinct from the "standard" GBM in terms of tumorigenesis pathway.

Adult↗
PubMed2005

Using LogitBoost classifier to predict protein structural classes.

Prediction of protein classification is an important topic in molecular biology. This is because it is able to not only provide useful information from the viewpoint of structure itself, but also greatly stimulate the characterization of many other features of proteins that may be closely correlated with their biological functions. In this paper, the LogitBoost, one of the boosting algorithms developed recently, is introduced for predicting protein structural classes. It performs classification using a regression scheme as the base learner, which can handle multi-class problems and is particularly superior in coping with noisy data. It was demonstrated that the LogitBoost outperformed the support vector machines in predicting the structural classes for a given dataset, indicating that the new classifier is very promising. It is anticipated that the power in predicting protein structural classes as well as many other bio-macromolecular attributes will be further strengthened if the LogitBoost and some other existing algorithms can be effectively complemented with each other.

Animals↗
PubMedDate not supplied

Blind and naive classification of toxicity by fish chromatophores.

Cellular and molecular pathways involved in the ability of animals to change color have been studied previously as biosensors and cytosensors of active and toxic agents, but such studies generally have been limited to just a few standardized agents. Here we describe the performance of cultured chromatophore pigment cells from the fin tissue of Siamese fighting fish as sensors of toxic agents under blind sampling conditions at the September 2002 EILATox-Oregon Workshop. Detection was accomplished by monitoring motor protein-mediated movements of cellular pigment in chromatophores at both the gross population level as well as in singly imaged cells. Pigment responses were recorded both during the exposure of chromatophores to each blind sample as well as afterwards when the cells were examined for after-effects by challenging them with clonidine, an adrenergic drug that induces standardized pigment movements. After recording all results and upon breaking the key to reveal the identities of the toxic agents, it was found that all of the toxic samples in the study had been distinguished accurately from non-toxic controls that were included among the blind samples. Furthermore, it was revealed that most of the toxic agents detected had never before been tested or calibrated against chromatophores, demonstrating that detection can be achieved under naive conditions that have not been optimized for the analysis of any particular toxic agent. Finally, by organizing the results into categories of pigment responses, a binary classification tree was generated that distinguished each toxic agent as having a distinct response pattern from the others. Thus, chromatophore-based cytosensors can discover toxicity in the absence of prior knowledge of the agent in question, and the categories of responses of the cells can be used to distinguish one toxic agent from another.

Animals↗
PubMed1994

An approach to work-up of dysmorphic patients: clinical, cytogenetic, and molecular aspects.

In view of recent advancement in the field of medical genetics, one approach to work-up a dysmorphic patient is to focus on how to study the patient clinically, cytogenetically, and molecularly. A clear understanding about major and minor anomalies, classification and terminologies of errors of morphogenesis, history taking, physical examination, laboratory studies including molecular cytogenetic techniques, genomic imprinting, uniparental disomy, and mosaicism is essential. Several clinical cases from my own experience are provided to illustrate my approach to work-up of dysmorphic patients. Case 1 was a newborn with multiple congenital anomalies (MCA) and a de novo dup (1) (pter-->q25::q12-->qter). Fluorescent in situ hybridization (FISH) unequivocally identified the duplicated region. Case 2 was a stillborn who had frontonasal dysplasia, arrhinencephaly, and other MCA with 46,XX,-7,+der(7), t(2;7) (q31;q36)mat. Her MCA were due to combined effect of trisomy 2q and monosomy 7q. This case helped to define the physical mapping of the critical region for a mild form of holoprosencephaly to 7q36. Case 3 had a classic de Lange phenotype with genital abnormality and sex reversal (46,XX male). Presence of SRY suggests X-Y interchange during paternal meiosis I. Case 4 was a female with primary amenorrhea, short stature, and 45,X/46,X,idic(Y)/47,X,idic(Y),idic(Y). This case demonstrates the need for molecular analyses to confirm the cytogenetic interpretations and allowed the refinement of the breakpoint in the isodicentric Y and karyotype/phenotype correlations. Case 5 & 6 were half sibs with ambiguous genitalia, minor somatic abnormalities, and dup (X) (p21.2-->p22.11)mat. Limited extent of the Xp duplication in these cases allows assignment of the X-linked sex-reversal (SRVX) locus to Xp21.2-->p22.11.

Adolescent↗
PubMed2005

Phylogenetic relationships and evolutionary traits in Ranunculus s.l. (Ranunculaceae) inferred from ITS sequence analysis.

Ranunculus is a large genus with a worldwide distribution. Phylogenetic analyses of c. 200 species of Ranunculus s.l. based on sequences of the nrITS using maximum parsimony and Bayesian inference yielded high congruence with previous cpDNA restriction site analyses, but strongly contradict previous classifications. A large core clade including Ranunculus subg. Ranunculus, subg. Batrachium, subg. Crymodes p.p., Ceratocephala, Myosurus, and Aphanostemma is separated from R. subg. Ficaria, subg. Pallasiantha, subg. Coptidium, subg. Crymodes p.p., Halerpestes, Peltocalathos, Callianthemoides, and Arcteranthis. Within the core clade, 19 clades can be described with morphological and karyological features. Several sections are not monophyletic. Parallel evolution of morphological characters in adaptation to climatic conditions may be a reason for incongruence of molecular data and morphology-based classifications. In some mountainous regions, groups of closely related species may have originated from adaptive radiation and rapid speciation. Split decomposition analysis indicated complex patterns of relationship and suggested hybridization in the apomictic R. auricomus complex, R. subg. Batrachium, and the white-flowering European alpines. The evolutionary success of the genus might be due to a combination of morphological plasticity and adaptations, hybridization and polyploidy as important factors for regional diversification, and a broad range of reproductive strategies.

DNA, Plant↗
PubMed2005

Molecular phylogenetic evidence for the monophyly of Fritillaria and Lilium (Liliaceae; Liliales) and the infrageneric classification of Fritillaria.

We present phylogenetic analyses of 37 taxa of Fritillaria (Liliaceae), 15 species of Lilium, and several outgroup taxa from Liliaceae s.s. to investigate the generic delimitation of Fritillaria in relation to Lilium as well as infrageneric relationships within Fritillaria. We used DNA sequences from the maturase-coding plastid matK gene and the trnK intron, the intron of the ribosomal protein-coding rpl16 plastid gene, and the nuclear ribosomal internal transcribed spacers (ITS). Phylogenetic analysis using maximum parsimony defined Fritillaria and Lilium (the latter including Nomocharis) as sister taxa. Fritillaria sections Fritillaria and Liliorhiza are supported in part, and some of the most enigmatic species usually included in Fritillaria (sections Petilium and Theresia and the monotypic genus Korolkowia) are closely related. The results support the new classification of Fritillaria proposed by Rix. We postulate independent origins of the underground bulbils found in Fritillaria davidii and the remainder of subgenus Liliorhiza.

Base Sequence↗