Denis Wilson Robertson
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ABSTRACT:
SUBMITTER: Bull D
PROVIDER: S-EPMC1363962 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The Hill-Robertson effect describes how, in a finite panmictic diploid population, selection at one diallelic locus reduces the fixation probability of a selectively favoured allele at a second, linked diallelic locus. Here we investigate the influence of population structure on the Hill-Robertson effect in a population of size N. We model population structure as a network by assuming that individuals occupy nodes on a graph connected by edges that link members who can reproduce with each other. Three regular networks (fully connected, ring and torus), two forms of scale-free network and a star are examined. We find that (i) the effect of population structure on the probability of fixation of the favourable allele is invariant for regular structures, but on some scale-free networks and a star, this probability is greatly reduced; (ii) compared to a panmictic population, the mean time to fixation of the favoured allele is much greater on a ring, torus and linear scale-free network, but much less on power-2 scale-free and star networks; (iii) the likelihood with which each of the four possible haplotypes eventually fix is similar across regular networks, but scale-free populations and the star are consistently less likely and much faster to fix the optimal haplotype; (iv) increasing recombination increases the likelihood of fixing the favoured haplotype across all structures, whereas the time to fixation of that haplotype usually increased, and (v) star-like structures were overwhelmingly likely to fix the least fit haplotype and did so significantly more rapidly than other populations. Last, we find that small (N < 64) panmictic populations do not exhibit the scaling property expected from Hill & Robertson (1966 Genet. Res. 8, 269-294. (doi:10.1017/S0016672300010156)).
| S-EPMC8074956 | biostudies-literature
Project description:Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype (high forehead, frontal bossing, large eyebrows, medially flaring and sparse in the middle part, hypertelorism, deep set but large eyes, large and uplifted ear lobes, with a central depression, saddle nose with prominent rounded nasal tip, prominent columella, open mouth, with M-shaped upper lip, frequent smiling, and a prominent but narrow and triangular pointed chin), moderate-to-severe intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease (HSCR), genitourinary anomalies (in particular hypospadias in males), congenital heart defects, agenesis of the corpus callosum and eye anomalies. The prevalence of MWS is currently unknown, but 171 patients have been reported so far. It seems probable that MWS is under-diagnosed, particularly in patients without HSCR. MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1). To date, over 100 deletions/mutations have been reported in patients with a typical phenotype; they are frequently whole gene deletions or truncating mutations, suggesting that haploinsufficiency is the main pathological mechanism. Studies of genotype-phenotype analysis show that facial gestalt and delayed psychomotor development are constant clinical features, while the frequent and severe congenital malformations are variable. In a small number of patients, unusual mutations can lead to an atypical phenotype. The facial phenotype is particularly important for the initial clinical diagnosis and provides the hallmark warranting ZEB2 mutational analysis, even in the absence of HSCR. The majority of MWS cases reported so far were sporadic, therefore the recurrence risk is low. Nevertheless, rare cases of sibling recurrence have been observed. Congenital malformations and seizures require precocious clinical investigation with intervention of several specialists (including neonatologists and pediatricians). Psychomotor development is delayed in all patients, therefore rehabilitation (physical therapy, psychomotor and speech therapy) should be started as soon as possible.
| S-EPMC2174447 | biostudies-literature
Project description:Theileria orientalis strain:Robertson Genome sequencing and assembly
| PRJNA325069 | ENA
Project description:Hill-Robertson interference (HRi) is expected to reduce the efficiency of natural selection when two or more linked selected sites do not segregate freely, but no attempt has been done so far to quantify the overall impact of HRi on the rate of adaptive evolution for any given genome. In this work, we estimate how much HRi impedes the rate of adaptive evolution in the coding genome of Drosophila melanogaster. We compiled a data set of 6,141 autosomal protein-coding genes from Drosophila, from which polymorphism levels in D. melanogaster and divergence out to D. yakuba were estimated. The rate of adaptive evolution was calculated using a derivative of the McDonald-Kreitman test that controls for slightly deleterious mutations. We find that the rate of adaptive amino acid substitution at a given position of the genome is positively correlated to both the rate of recombination and the mutation rate, and negatively correlated to the gene density of the region. These correlations are robust to controlling for each other, for synonymous codon bias and for gene functions related to immune response and testes. We show that HRi diminishes the rate of adaptive evolution by approximately 27%. Interestingly, genes with low mutation rates embedded in gene poor regions lose approximately 17% of their adaptive substitutions whereas genes with high mutation rates embedded in gene rich regions lose approximately 60%. We conclude that HRi hampers the rate of adaptive evolution in Drosophila and that the variation in recombination, mutation, and gene density along the genome affects the HRi effect.
| S-EPMC4794616 | biostudies-literature
Project description:X and Y chromosomes differ in effective population size (Ne ), rates of recombination, and exposure to natural selection, all of which can affect patterns of genetic diversity. On Y chromosomes with suppressed recombination, natural selection is expected to eliminate linked neutral variation, and lower the Ne of Y compared to X chromosomes or autosomes. However, female-biased sex ratios and high variance in male reproductive success can also reduce Y-linked Ne , making it difficult to infer the causes of low Y-diversity. Here, we investigate the factors affecting levels of polymorphism during sex chromosome evolution in the dioecious plant Rumexhastatulus (Polygonaceae). Strikingly, we find that neutral diversity for genes on the Y chromosome is, on average, 2.1% of the value for their X-linked homologs, corresponding to a chromosome-wide reduction of 93% compared to the standard neutral expectation. We demonstrate that the magnitude of this diversity loss is inconsistent with reduced male Ne caused by neutral processes. Instead, using forward simulations and estimates of the distribution of deleterious fitness effects, we show that Y chromosome diversity loss can be explained by purifying selection acting in aggregate over a large number of genetically linked sites. Simulations also suggest that our observed level of Y-diversity is consistent with the joint action of purifying and positive selection, but only for models in which there were fewer constrained sites than we empirically estimated. Given the relatively recent origin of R. hastatulus sex chromosomes, our results imply that Y-chromosome degeneration in the early stages may be largely driven by selective interference rather than by neutral genetic drift of silenced Y-linked genes.
| S-EPMC5629332 | biostudies-literature
Project description:Minimally invasive operative techniques and enhanced recovery after surgery (ERAS) protocols have transformed clinical practice and made it possible to perform increasingly complex oncologic procedures in the ambulatory setting, with recovery at home after a single overnight stay. Capitalizing on these changes, Memorial Sloan Kettering Cancer Center's Josie Robertson Surgery Center (JRSC), a freestanding ambulatory surgery facility, was established to provide both outpatient procedures and several surgeries that had previously been performed in the inpatient setting, newly transitioned to this ambulatory extended recovery (AXR) model. However, the JRSC core mission goes beyond rapid recovery, aiming to be an innovation center with a focus on superlative patient experience and engagement, efficiency, and data-driven continuous improvement. Here, we describe the JRSC genesis, design, care model, and outcome tracking and quality improvement efforts to provide an example of successful, patient-centered surgical care for select patients undergoing relatively complex procedures in an ambulatory setting.
| S-EPMC8285049 | biostudies-literature
Project description:Three new species of Brachystomellidae from high altitude fields of southeast Brazil are described and illustrated and additions made to the description of Micronella porcus (Denis, 1933). The new species are Neorganella rotundatae sp. n., the second for the genus, Micronella itacaman sp. n. and Micronella longisensilla sp. n. Diagnosis of the genera have been extended. An identification key to the genus Micronella Arlé, 1959 is provided.
| S-EPMC3713336 | biostudies-literature
Project description:BackgroundMowat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16?years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children.ResultsIn newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7?years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7?years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build.ConclusionsThese charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.
| S-EPMC7294656 | biostudies-literature
Project description:Wilson disease (WD) is an autosomal-recessive disorder of hepatocellular copper deposition caused by pathogenic variants in the copper-transporting gene, ATP7B. Early detection and treatment are critical to prevent lifelong neuropsychiatric, hepatic, and systemic disabilities. Due to the marked heterogeneity in age of onset and clinical presentation, the diagnosis of Wilson disease remains challenging to physicians today. Direct sequencing of the ATP7B gene is the most sensitive and widely used confirmatory testing method, and concurrent biochemical testing improves diagnostic accuracy. More than 600 pathogenic variants in ATP7B have been identified, with single-nucleotide missense and nonsense mutations being the most common, followed by insertions/deletions, and, rarely, splice site mutations. The prevalence of Wilson disease varies by geographic region, with higher frequency of certain mutations occurring in specific ethnic groups. Wilson disease has poor genotype-phenotype correlation, although a few possible modifiers have been proposed. Improving molecular genetic studies continue to advance our understanding of the pathogenesis, diagnosis, and screening for Wilson disease.
| S-EPMC5648646 | biostudies-literature