PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “digital phenotyping”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 37 records · Page 2Linked to original sources
PubMed2001

Inhibition of polarizing activity in the anterior limb bud is regulated by extracellular factors.

Anterior-posterior patterning of the developing limb is largely viewed as a function of polarizing activity. Recent evidence in polydactylous mutants, however, indicates that development of proper pattern also requires the involvement of inhibitory pathways in the anterior limb that prevent secondary polarizing zone formation, thus limiting the number of digits produced. We report the novel finding that grafts of extracellular matrix from the Mouse Posterior Limb Bud-4 cell line can induce supernumerary digits, including digits with posterior phenotype, from anterior chick limb mesenchyme. Unlike previously described mechanisms of pattern specification during limb development, it is shown that the extracellular matrix effect is not associated with release of an active signal. Rather, evidence is presented suggesting that heparan sulfate moieties in extracellular matrix grafts bind an endogenous, extracellular factor involved in inhibition of anterior polarizing activity, leading to derepression of the anterior limb and induction of polarizing zone marker genes including Sonic hedgehog and Bone morphogenetic protein-2.

Animals↗
PubMed2005

Quantitative genetics and behavioural correlates of digit ratio in the zebra finch.

A recent study on a captive zebra finch population suggested that variation in digit ratio (i.e. the relative length of the second to the fourth toe) might be an indicator of the action of sex steroids during embryo development, as is widely assumed for human digits. Zebra finch digit ratio was found to vary with offspring sex, laying order of eggs within a clutch, and to predict aspects of female mating behaviour. Hence, it was proposed that the measurement of digit ratio would give insights into how an individual's behaviour is shaped by its maternal environment. Studying 500 individuals of a different zebra finch population I set out to: (1) determine the proximate causes of variation in digit ratio by means of quantitative genetics and (2) to search for phenotypic and genetic correlations between digit ratio, sexual behaviour and aspects of fitness. In contrast to the earlier study, I found no sexual dimorphism in digit ratio and no effect of either laying order or experimentally altered hatching order on digit ratio. Instead, I found that variation in digit ratio was almost entirely additive genetic, with heritability estimates ranging from 71 to 84%. The rearing environment (from egg deposition to independence) explained an additional 5-6% of the variation in digit ratio, but there was no indication of any maternal effects transmitted through the egg. I found highly significant phenotypic correlations (and genetic correlations of similar size) between digit ratio and male song rate (positive correlation) as well as between digit ratio and female hopping activity in a choice chamber (negative correlation). Rather surprisingly, the strength of these correlations differed significantly between subsequent generations of the same population, illustrating how quickly such correlations can appear and disappear probably due to genotype-environment interactions.

Animals↗
PubMed2006

Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus).

The length ratio between individual digits differs between males and females in humans, other mammals, lizards, and one bird species. Sexual dimorphism in digit ratios and variation among individuals of the same sex may depend on differential exposure to androgens and estrogens during embryonic life. Organizational effects of sex hormones could cause the observed correlations between digit ratios and diverse phenotypic traits in humans. However, no study has investigated experimentally the effect of prenatal estrogens on digit ratios. We analyzed the effect of estradiol injection in ring-necked pheasant (Phasianus colchicus) eggs on digit ratios. Males from control eggs had higher ratios between the second or third and the fourth digit of the right foot compared to females. Estradiol-treated eggs produced males with lower (feminized) right foot second to fourth digit ratio. Thus, we provided the first experimental evidence that prenatal exposure to physiologically high estrogen levels affects bird digit ratios.

Animals↗
PubMedDate not supplied

Measuring the facial phenotype of individuals with prenatal alcohol exposure: correlations with brain dysfunction.

The purpose of this report is to demonstrate how to measure the magnitude of expression of the fetal alcohol syndrome (FAS) facial phenotype using the new 4-Digit Diagnostic Code and the previously developed D-score and to demonstrate how these two measures of the FAS facial phenotype correlate with brain function and structure; correlations that fail to be identified by the older gestalt method of facial measurement. The D-score and the facial component of the 4-Digit Diagnostic Code quantitatively measure the magnitude of expression of the FAS facial phenotype using three facial features (palpebral fissure length, philtrum smoothness, and upper lip thinness). These facial measurement systems were developed by the Washington State FAS Diagnostic and Prevention Network (FAS DPN) of clinics and are used to screen and diagnose the facial component of FAS for all patients evaluated in the network of clinics (1500 to date). The 4-Digit Diagnostic Code is a comprehensive diagnostic system developed by the FAS DPN in 1997 to diagnose the full spectrum of outcomes among patients with prenatal alcohol exposure. The four digits reflect the magnitude of expression of the four key diagnostic features of FAS in the following order: (1) growth deficiency; (2) the FAS facial phenotype; (3) brain dysfunction; (4) gestational alcohol exposure. The 4-Digit Diagnostic Code was developed to overcome the subjective, highly variable gestalt method of diagnosis that has been used as the standard to date, worldwide. Prior to the development of the 4-Digit Diagnostic Code, the first 445 patients evaluated in the FAS DPN were diagnosed using the gestalt method. For research purposes, their gestalt diagnoses were transformed into 4-Digit Diagnostic Codes, presenting a unique opportunity to directly compare the two diagnostic methods. When the facial phenotype was measured using the 4-Digit Diagnostic Code or D-score, the magnitude of expression of the FAS facial phenotype was significantly correlated with structural, neurologic, and functional measures of brain damage, and the phenotype of those receiving a 4-Digit Diagnosis of FAS showed little variability. When the gestalt method of diagnosis was used, the magnitude of expression of the FAS facial phenotype did not correlate with structural, neurologic and functional measures of brain damage, and the facial phenotype of those receiving a gestalt diagnosis of FAS was highly variable. The 4-Digit Diagnostic Code and D-score thus provide more precise and accurate measures of the FAS facial phenotype and reveal important correlations with brain structure and function, suggesting that intermediate expressions of the FAS facial phenotype may serve as important risk factors for brain damage caused by prenatal alcohol exposure.

Adolescent↗
PubMed2005

Real ribozymes suggest a relaxed error threshold.

The error threshold for replication, the critical copying fidelity below which the fittest genotype deterministically disappears, limits the length of the genome that can be maintained by selection. Primordial replication must have been error-prone, and so early replicators are thought to have been necessarily short. The error threshold also depends on the fitness landscape. In an RNA world, many neutral and compensatory mutations can raise the threshold, below which the functional phenotype, rather than a particular sequence, is still present. Here we show, on the basis of comparative analysis of two extensively mutagenized ribozymes, that with a copying fidelity of 0.999 per digit per replication the phenotypic error threshold rises well above 7,000 nucleotides, which permits the selective maintenance of a functionally rich riboorganism with a genome of more than 100 different genes, the size of a tRNA. This requires an order of magnitude of improvement in the accuracy of in vitro-generated polymerase ribozymes. Incidentally, this genome size coincides with that estimated for a minimal cell achieved by top-down analysis, omitting the genes dealing with translation.

Base Pairing↗
PubMed2005

RNAi as a tool to study cell biology: building the genome-phenome bridge.

In the few short years since its discovery, RNA interference (RNAi) has revolutionized the functional analysis of genomes: both technical and conceptual approaches to the investigation of gene function are being transformed as a result of this new technology. Genome-scale RNAi analyses have already been performed in the model organisms Caenorhabditis elegans (in vivo) and Drosophila melanogaster (in cell lines), ushering in a new era of RNAi-based approaches to probing the inner workings of the cell. The transformation of complex phenotypic data into mineable 'digitized' formats is fostering the emergence of a new area of bioinformatics related to the phenome.

Animals↗
PubMed2002

Visual predators select for crypticity and polymorphism in virtual prey.

Cryptically coloured animals commonly occur in several distinct pattern variants. Such phenotypic diversity may be promoted by frequency-dependent predation, in which more abundant variants are attacked disproportionately often, but the hypothesis has never been explicitly tested. Here we report the first controlled experiment on the effects of visual predators on prey crypticity and phenotypic variance, in which blue jays (Cyanocitta cristata) searched for digital moths on computer monitors. Moth phenotypes evolved via a genetic algorithm in which individuals detected by the jays were much less likely to reproduce. Jays often failed to detect atypical cryptic moths, confirming frequency-dependent selection and suggesting the use of searching images, which enhance the detection of common prey. Over successive generations, the moths evolved to become significantly harder to detect, and they showed significantly greater phenotypic variance than non-selected or frequency-independent selected controls.

Algorithms↗
PubMed2006

Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study.

Oral-facial-digital syndrome type 1 (OFD1) is characterised by an X linked dominant mode of inheritance with lethality in males. Clinical features include facial dysmorphism with oral, tooth, and distal abnormalities, polycystic kidney disease, and central nervous system malformations. Large interfamilial and intrafamilial clinical variability has been widely reported, and 18 distinct mutations have been previously reported within OFD1. A French and Belgian collaborative study collected 25 cases from 16 families. OFD1 was analysed using direct sequencing and phenotype-genotype correlation was performed using chi2 test. X inactivation studies were performed on blood lymphocytes. In 11 families, 11 novel mutations, including nine frameshift, one nonsense, and one missense mutation were identified, which spanned nine different exons. A combination of our results with previously reported cases showed that the majority of mutations (65.5%) was located in exons 3, 8, 9, 13, and 16. There was phenotype-genotype correlation between (a) polycystic kidney disease and splice mutations; (b) mental retardation and mutations located in exons 3, 8, 9, 13, and 16; and (c) tooth abnormalities and mutations located in coiled coil domains. Comparing the phenotype of the families with a pathogenic mutation to families with absence of OFD1 mutation, polycystic kidneys and short stature were significantly more frequent in the group with no OFD1 mutation, whereas lingual hamartomas were significantly more frequent in the group with OFD1 mutation. Finally, an X inactivation study showed non-random X inactivation in a third of the samples. Differential X inactivation between mothers and daughters in two families with high intrafamilial variability was of particular interest. Slight phenotype-genotype correlations were established, and X inactivation study showed that skewed X inactivation could be partially involved in the pathogenesis of intrafamilial clinical variability.

Adult↗
PubMed2004

Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR.

Lenz microphthalmia is inherited in an X-linked recessive pattern and comprises microphthalmia, mental retardation, and skeletal and other anomalies. Two loci associated with this syndrome, MAA (microphthalmia with associated anomalies) and MAA2, are situated respectively at Xq27-q28 (refs. 1,2) and Xp11.4-p21.2 (ref. 3). We identified a substitution, nt 254C-->T; P85L, in BCOR (encoding BCL-6-interacting corepressor, BCOR) in affected males from the family with Lenz syndrome previously used to identify the MAA2 locus. Oculofaciocardiodental syndrome (OFCD; OMIM 300166) is inherited in an X-linked dominant pattern with presumed male lethality and comprises microphthalmia, congenital cataracts, radiculomegaly, and cardiac and digital abnormalities. Given their phenotypic overlap, we proposed that OFCD and MAA2-associated Lenz microphthalmia were allelic, and we found different frameshift, deletion and nonsense mutations in BCOR in seven families affected with OFCD. Like wild-type BCOR, BCOR P85L and an OFCD-mutant form of BCOR can interact with BCL-6 and efficiently repress transcription. This indicates that these syndromes are likely to result from defects in alternative functions of BCOR, such as interactions with transcriptional partners other than BCL-6. We cloned the zebrafish (Danio rerio) ortholog of BCOR and found that knock-down of this ortholog caused developmental perturbations of the eye, skeleton and central nervous system consistent with the human syndromes, confirming that BCOR is a key transcriptional regulator during early embryogenesis.

Abnormalities, Multiple↗
PubMedDate not supplied

Regression analysis of digital ridge counts on pattern intensity index: a developmental interpretation.

Regression analyses of digital ridge counts on pattern intensity index (PII) are performed on data from three populations. The results for two Papua New Guinean populations (608 subjects from Karkar Island and 397 from Lufa sub District) are compared with those for a dermatoglyphically very different population from the Faroe Islands (296 subjects). Digital relationships are examined within each population. Equating the statistical regression of digital ridge counts with the embryological regression of apical volar pads, some biological interpretations of the findings are suggested. The results indicate that developmental fields across the embryological hand interact with genotype to produce digital differences in dermatoglyphic phenotype.

Denmark↗
PubMed1993

The role of Hox genes in limb development.

In order to directly test the function of Hox genes in vertebrate limb development, we have employed a replication-competent retroviral vector to express the genes ectopically in developing chick limb buds. It has been hypothesized that the sum of all Hox genes expressed in a developing region forms a "Hox code" which determines the fate of structures arising from that region. When the Hox code of the of the anlage of the chicken hind limb digit I is altered to match that of digit II, the resulting foot has two similar toes both resembling digit II in morphology. This suggests that the misexpressed gene, Hox-4.6, plays a role in controlling digit morphological identity. Other phenotypes observed in the proximal parts of the hind limb and in similar experiments in the wing also lend support to this interpretation. The retroviral vector system used in these experiments provides a powerful approach for testing the function of genes in limb development.

Amino Acid Sequence↗
PubMed2002

Postaxial polydactyly type A/B (PAP-A/B) is linked to chromosome 19p13.1-13.2 in a Chinese kindred.

Postaxial polydactyly is characterised by fifth digit duplications in hands and/or feet. Two phenotypic varieties have been described. In type A, the extra digit is well formed and articulates with the fifth or an extra metacarpal. A rudimentary extra fifth digit characterises type B. Mutations in the GLI3 gene are associated with postaxial polydactyly in some families and a second locus has been identified on chromosome 13 but the majority of cases remain unexplained. We report here a third locus for postaxial polydactyly on chromosome 19p13.1-13.2 in a large Chinese kindred with a combination of type A and B. Two-point linkage analysis showed the highest LOD score (Z(max) = 5.85 at theta; = 0 cM) at marker D19S221. Recombination events with markers D19S1165 and D19S929 define the critical region for this postaxial polydactyly locus to a region of 4.3 cM on the genetic map.

China↗
PubMed2005

Experimental manipulation of yolk testosterone affects digit length ratios in the ring-necked pheasant (Phasianus colchicus).

In humans, most of the mammals and one bird species studied so far, the relative length of individual digits is sexually dimorphic. Most studies of humans have been concerned with the ratio between second (2D) and fourth digits (4D), whereas some studies of humans and other mammals have also investigated other digit ratios. Inter- and intra-sexual variation in 2D:4D may depend on differential exposure to androgens during embryonic life, and the genetic mechanisms linking 2D:4D to androgens may be mediated by Hox genes. Because Hox genes are conserved in vertebrates, similar patterns of variation in digit ratios might be expected across vertebrate classes. The observation of correlations between digit ratios and physiological, psychological and performance traits in humans has generated interest in exploring the possibility that digit ratios are a marker of embryonic exposure to androgens, which have diverse consequences on several phenotypic traits. However, the hypothesis that digit ratios depend on androgen effects during development has never been tested experimentally. In this study, we increased testosterone concentration in ring-necked pheasant eggs and measured length ratios between the second, third and fourth digits of both feet in fully grown offspring. Females from testosterone-injected eggs had larger 2D:3D in the left foot, whereas this was not the case in males. The other digit ratios were unaffected by hormone treatment in both sexes. However, digit ratios showed no sexual dimorphism among controls. Thus, present results are consistent with the hypothesis that variation in testosterone levels during development affects digit ratios.

Animals↗
PubMed1995

Unique de novo interstitial deletion of chromosome 17, del(17) (q23.2q24.3) in a female newborn with multiple congenital anomalies.

We describe a newborn with a novel interstitial deletion of the long arm of chromosome 17 [del (17) (q23.2q24.3)] who died on day of life 17 during a recurrent apneic episode. Her phenotype included severe growth retardation, multiple facial anomalies, maldeveloped oralpharyngeal structures, and digital and widespread skeletal anomalies. This patient's phenotype was compared to two other reported patients with deletion 17q with minor clinical overlap consistent with a unique deletion.

Abnormalities, Multiple↗
PubMed2026

Two Saccharopolyspora isolates from archaeological excavation sites: polyphasic taxonomy, biosynthetic potential, bioactivity profiling and description of Saccharopolyspora antiqui sp. nov.

Archaeological excavation sites represent underexplored microbial habitats with the potential to recover taxonomically and biotechnologically valuable actinomycetes. In this study, two Saccharopolyspora strains, 5N708T and 5N102, were isolated from soil samples collected from the Gaziantep-Doliche-Dülük and Bitlis-Ahlat-Selçuklu Cemetery archaeological excavation sites in Türkiye. A polyphasic taxonomic approach, including 16S rRNA gene sequencing, phylogenetic and phylogenomic analyses, average nucleotide identity, digital DNA-DNA hybridization, phenotypic characterization, and chemotaxonomic analyses, showed that strain 5N708T represents a novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora antiqui sp. nov. is proposed, whereas strain 5N102 was assigned to Saccharopolyspora elongata. Both isolates were further evaluated for their antimicrobial, antioxidant, and cytotoxic activities, and their biosynthetic potential was investigated by genome mining. Both strains showed activity against Staphylococcus aureus, with strain 5N708T producing the larger inhibition zone. Strain 5N102 exhibited markedly stronger antioxidant activity than strain 5N708T in radical scavenging, ferric reducing antioxidant power, and reducing power assays. In contrast, strain 5N708T showed more promising cytotoxic activity, with relative selectivity toward MIA PaCa-2 pancreatic cancer cells compared with HEK293 cells after prolonged incubation. Genome mining revealed multiple biosynthetic gene clusters in both isolates, supporting their capacity to produce secondary metabolites. These findings indicate that archaeological soils are promising reservoirs of taxonomically novel and biologically active Saccharopolyspora strains.

Saccharopolyspora↗
PubMed2001

Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse.

Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.

Animals↗