Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.     

Early phylogenetic estimate of the effective reproduction number of SARS-CoV-2

To reconstruct the evolutionary dynamics of the 2019 novel-coronavirus recently causing an outbreak in Wuhan, China, 52 SARS-CoV-2 genomes available on 4 February 2020 at Global Initiative on Sharing All Influenza Data were analyzed. The two models used to estimate the reproduction number (coalescent-based exponential growth and a birth-death skyline method) indicated an estimated mean evolutionary rate of 7.8 × 10⁻⁴ subs/site/year (range, 1.1 × 10⁻⁴-15 × 10⁻⁴) and a mean tMRCA of the tree root of 73 days. The estimated R value was 2.6 (range, 2.1-5.1), and increased from 0.8 to 2.4 in December 2019. The estimated mean doubling time of the epidemic was between 3.6 and 4.1 days. This study proves the usefulness of phylogeny in supporting the surveillance of emerging new infections even as the epidemic is growing.     

免疫透射比浊法测定血清免疫球蛋白

本文报道免疫透射比浊法测定血清免疫球蛋白,批内CV小于2.0％,批间CV小于3.5％,表明该法简便,快速,精密度和准确度高,重复性好。     

Setting out the frame conditions for feasible use of FFPE derived RNA

Introduction

The usage of formalin-fixed paraffin embedded (FFPE) tissue is characterized by its long shelf-life and simple handling. Therefore it is the most commonly available tissue specimen in routine diagnostics and histological studies. Formaldehyde fixation may result in RNA degradation and cross linking with proteins, while storage conditions also affect RNA integrity. The present study was designed to investigate the influence of these factors on RNA analysis.

A computer-interfaced photometer and systematic spacing of duplicates to control within-plate enzyme-immunoassay variation

A Multiskan photometer for reading microtiter plate enzyme immunoassays was linked with a time sharing computer to facilitate control of assay variation and analysis of results. The interface that converted photometer output to RS-232-C format required changes to divide the output into segments short enough for input to the computer. To measure within-plate variation and investigate how the method of allocating sample duplicates to plate wells may affect the estimation of sample variance, uniformity tests were conducted with 47 plates. Coefficients of variation (CV) among wells within-plates ranged from 4.6 to 20.7% and in two-thirds of the plates exceeded 10%. Duplicates allocated to adjacent wells (method 1) gave consistently higher CV for sample means than duplicates allocated to opposite plate quadrants (method 2). In general, the CV by method 2 was about 30% smaller than that by method 1. Analysis of variance confirmed the effectiveness of the quadrant pattern of duplicate allocation as a method of controlling variation that arises from well position effects.     

A geometric morphometric study of regional differences in the ontogeny of the modern human facial skeleton

This study examines interpopulation variations in the facial skeleton of 10 modern human populations and places these in an ontogenetic perspective. It aims to establish the extent to which the distinctive features of adult representatives of these populations are present in the early post natal period and to what extent population differences in ontogenetic scaling and allometric trajectories contribute to distinct facial forms. The analyses utilize configurations of facial landmarks and are carried out using geometric morphometric methods. The results of this study show that modern human populations can be distinguished based on facial shape alone, irrespective of age or sex, indicating the early presence of differences. Additionally, some populations have statistically distinct facial ontogenetic trajectories that lead to the development of further differences later in ontogeny. We conclude that population-specific facial morphologies develop principally through distinctions in facial shape probably already present at birth and further accentuated and modified to variable degrees during growth. These findings raise interesting questions regarding the plasticity of facial growth patterns in modern humans. Further, they have important implications in relation to the study of growth in the face of fossil hominins and in relation to the possibility of developing effective discriminant functions for the identification of population affinities of immature facial skeletal material. Such tools would be of value in archaeological, forensic and anthropological applications. The findings of this study underline the need to examine more deeply, and in more detail, the ontogenetic basis of other causes of craniometric variation, such as sexual dimorphism and hominin species differentiation.     

Restriction fragment differences between the genomes of the Oka varicella vaccine virus and American wild-type varicella-zoster virus

The Oka vaccine strains of varicella-zoster virus (VZV) have a significantly different BgII DNA restriction pattern from that of American wild-type isolates of VZV. This difference consists primarily of an additional BgII site, which lies within the BamHI "D" fragment. In conjunction with a study of the efficacy of an experimental Merck/Oka VZV vaccine, the area of the genome from which the most marked restriction pattern alteration arises was studied more closely to determine if there are other significant differences between the Oka strains and American wild-type strains. BamHI "D" fragments from the DNA of the Oka parent strain (the progenitor of the vaccine strain), the RIT/Oka vaccine strain (a derivative of the Oka parent strain), the Merck/Oka vaccine strain, and the EF strain (an American wild type), were submitted to extensive endonuclease digestion studies to ascertain if additional unique restriction sites are present in the Oka parent or vaccine strains. The extra BgII restriction site characteristic of the Merck/Oka vaccine strain is also present in the DNA of the parent virus as well as its derivatives and was therefore not produced by the "attenuation" process. No other novel sites were found in the Oka parent or Oka-derived strains in this section of the genome. The Merck/Oka vaccine strain of VZV, despite its Japanese origin, is therefore quite similar to circulating American varicella-zoster virus strains. Varicella-zoster virus DNA, at least in the area of the BamHI D fragment, also appears to be remarkably stable from strain to strain.     

The Origin and Evolution of Human T-Cell Lymphotropic Virus Types I and II

Studies on human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) are briefly reviewed from the viewpoint of molecular evolution, with special reference to the evolutionary rate and evolutionary relationships among these viruses. In particular, it appears that, in contrast to the low level of variability of HTLV-I among different isolates, individual isolates form quasispecies structures. Elucidating the mechanisms connecting these two phenomena will be one of the future problems in the study of the molecular evolution of HTLV-I and HTLV-II.     

Developmental expression of FOG-1/CPEB protein and its control in the Caenorhabditis elegans hermaphrodite germ line.

The specification of a germ cell as sperm or oocyte and determination of cell number remain unsolved questions in developmental biology. This paper examines Caenorhabditis elegans FOG-1, a CPEB-related RNA-binding protein that controls the sperm fate. We find that abundant FOG-1 protein is observed transiently in germ cells just prior to their expression of an early sperm-differentiation marker. As the germline tissue elongates, abundant FOG-1 appears more and more distally as sperm become specified, but disappears when the germ line switches to oogenesis. This dynamic pattern is controlled by both globally acting and germline-specific sex-determining regulators. Importantly, the extent of FOG-1 expression corresponds roughly to sperm number in wild-type and mutants, altering sperm number. By contrast, three other key regulators of the sperm/oocyte decision do not similarly correspond to sperm number. We suggest that FOG-1 is precisely modulated in both time and space to specify sperm fate and control sperm number.