Core Families Research Articles

Application of CNVPLUS-array custom microarray in genetic analysis of spinal muscular atrophy

To assess the application value of CNVPLUS-array for the genetic analysis of Spinal muscular atrophy (SMA). From June 2021 to December 2022, CNVPLUS-array technique was employed to test the SMN1 and SMN2 genes among peripheral blood samples from 17 suspected SMA patients, 18 core families with suspected SMA, and 25 healthy individuals. The results were compared with those of multiple ligation-dependent probe amplification (MLPA) assay. Samples with inconsistent results were subjected to nested PCR or comprehensive analysis of SMA. CNVPLUS-array has identified 35 SMA patients, 36 carriers, and 25 healthy individuals. In comparison, MLPA has identified 34 SMA patients, 36 carriers, and 26 healthy individuals. The two methods demonstrated a high consistency (Kappa = 0.968, P < 0.001). Additionally, CNVPLUS-array has identified one patient with compound heterozygous variants of SMN1 and one carrier with a [2+0] genotype. CNVPLUS-array not only can accurately determine the copy numbers of SMN1 and SMN2 genes, but also identify point mutations in SMN1 and [2+0] carriers, which has offered a new method for the genetic testing of SMA.

Medullary bundles in Caryophyllales: form, function, and evolution.

The occurrence of conducting vascular tissue in the pith (CVTP) of tracheophytes is noteworthy. Medullary bundles, one of the remarkable examples of CVTP, evolved multiple times across angiosperms, notably in the Caryophyllales. Yet, information on the occurrence of medullary bundles is fragmented, hampering our understanding of their structure-function relationships, and evolutionary implications. Using three plastid molecular markers (matK, rbcL, and rps16 intron), a phylogeny is constructed for 561 species of Caryophyllales, and anatomical data are assembled for 856 species across 40 families to investigate the diversity of medullary bundles, their function, evolution, and diversification dynamics. Additionally, correlated evolution between medullary bundles and successive cambia was tested. Medullary bundles are ancestrally absent in Caryophyllales and evolved in core and noncore families. They are structurally diverse (e.g. number, arrangement, and types of bundles) and functionally active throughout the plant's lifespan, providing increased hydraulic conductivity, especially in herbaceous plants. Acquisition of medullary bundles does not explain diversification rate heterogeneity but is correlated to a higher diversification rate. Disparate developmental pathways were found leading to rampant convergent evolution of CVTP in Caryophyllales. These findings indicate the diversification of medullary bundles and vascular tissues as another central theme for functional and comparative molecular studies in Caryophyllales.

Associations of the COVID-19 burden and various comorbidities of different ethnic groups in Israel: a cross-sectional study.

Coronavirus disease (COVID-19) is highly transmissible between human beings. We examined differences in the core families with COVID-19 severity and mortality and comorbidities between Arab and Jews and explored the factors associated with COVID-19 severity and mortality to find a genetic component. A cross-sectional study was conducted among 2240 COVID-19 patients (> 18 years of age) randomly selected by online panels and questionnaires in the native language (Hebrew or Arabic) during March 2021-June 2022. Multivariable linear regression models were used to assess correlations with COVID-19 disease severity and mortality. Overall, 1549 (69%) were Arabs and 691 (31%) were Jews. The proportion of participants who died from COVID-19 was higher among Arabs compared with Jews (66% vs. 59%), P < 0.001. The mean number of deaths from COVID-19 and patients with severe COVID-19 was higher in ultra-Orthodox Jewish, non-academic core families and those who lived in the city residence compared with secular, academic core families and who live in the village residence, P < 0.001. A multivariable linear regression model showed a significant association between metabolic, kidney, cardiovascular, and respiratory diseases with COVID-19 severity (B coefficient - 0.43, B coefficient - 0.53, B coefficient - 0.53, B coefficient - 0.42, respectively) and COVID-19 mortality (B coefficient - 0.51, B coefficient - 0.64, B coefficient - 0.67, B coefficient - 0.34, respectively), P < 0.001. COVID-19 severity and mortality were highly associated with comorbidities, ethnicity, social and environmental factors. Furthermore, we believe that genetic factors also contribute to the increase in COVID-19 severity and mortality and the differences rates of these between Arabs and Jews in Israel.

Exploring Living Arrangements as a Predictor of Canadians' Illicit Drug Use: Quantitative Findings From the Canadian Community Health Survey.

Objectives: About four percent of Canadians used illegal drugs in 2019, but it remains unknown whether their living arrangements are a relevant factor. Methods: We use the public version of the 2015-2016 Canadian Community Health Survey Annual Component. The binary logit model and complementary log-log model are applied to investigate to what extent living arrangements predict Canadians' recent illicit drug use. Results: Living alone is significantly associated with Canadians' illicit drug use. For young and older Canadians, those living with spouses/partners, children, or both are less likely to use illicit drugs than their solo-living counterparts. Middle-aged Canadians who lived with spouses/partners only or with children have significantly lower likelihoods of using illicit drugs compared to those living alone. Additionally, differences between men and women have been found. Spouses/partners and children play more positive roles for young and middle-aged women than for men. Conclusion: Our findings suggest that living with core families is a type of collectivity that may have positive effects on Canadians' health behaviours compared to those living alone, who, therefore, need more attention from health officials.

DNA methylation signatures of duplicate gene evolution in angiosperms.

Gene duplication is a source of evolutionary novelty. DNA methylation may play a role in the evolution of duplicate genes (paralogs) through its association with gene expression. While this relationship has been examined to varying extents in a few individual species, the generalizability of these results at either a broad phylogenetic scale with species of differing duplication histories or across a population remains unknown. We applied a comparative epigenomics approach to 43 angiosperm species across the phylogeny and a population of 928 Arabidopsis (Arabidopsis thaliana) accessions, examining the association of DNA methylation with paralog evolution. Genic DNA methylation was differentially associated with duplication type, the age of duplication, sequence evolution, and gene expression. Whole genome duplicates were typically enriched for CG-only gene-body methylated or unmethylated genes, while single-gene duplications were typically enriched for non-CG methylated or unmethylated genes. Non-CG methylation, in particular, was characteristic of more recent single-gene duplicates. Core angiosperm gene families differentiated into those which preferentially retain paralogs and 'duplication-resistant' families, which convergently reverted to singletons following duplication. Duplication-resistant families that still have paralogous copies were, uncharacteristically for core angiosperm genes, enriched for non-CG methylation. Non-CG methylated paralogs had higher rates of sequence evolution, higher frequency of presence-absence variation, and more limited expression. This suggests that silencing by non-CG methylation may be important to maintaining dosage following duplication and be a precursor to fractionation. Our results indicate that genic methylation marks differing evolutionary trajectories and fates between paralogous genes and have a role in maintaining dosage following duplication.

Categorizing 161 plant (streptophyte) mitochondrial group II introns into 29 families of related paralogues finds only limited links between intron mobility and intron-borne maturases

Group II introns are common in the two endosymbiotic organelle genomes of the plant lineage. Chloroplasts harbor 22 positionally conserved group II introns whereas their occurrence in land plant (embryophyte) mitogenomes is highly variable and specific for the seven major clades: liverworts, mosses, hornworts, lycophytes, ferns, gymnosperms and flowering plants. Each plant group features “signature selections” of ca. 20–30 paralogues from a superset of altogether 105 group II introns meantime identified in embryophyte mtDNAs, suggesting massive intron gains and losses along the backbone of plant phylogeny. We report on systematically categorizing plant mitochondrial group II introns into “families”, comprising evidently related paralogues at different insertion sites, which may even be more similar than their respective orthologues in phylogenetically distant taxa. Including streptophyte (charophyte) algae extends our sampling to 161 and we sort 104 streptophyte mitochondrial group II introns into 25 core families of related paralogues evidently arising from retrotransposition events. Adding to discoveries of only recently created intron paralogues, hypermobile introns and twintrons, our survey led to further discoveries including previously overlooked “fossil” introns in spacer regions or e.g., in the rps8 pseudogene of lycophytes. Initially excluding intron-borne maturase sequences for family categorization, we added an independent analysis of maturase phylogenies and find a surprising incongruence between intron mobility and the presence of intron-borne maturases. Intriguingly, however, we find that several examples of nuclear splicing factors meantime characterized simultaneously facilitate splicing of independent paralogues now placed into the same intron families. Altogether this suggests that plant group II intron mobility, in contrast to their bacterial counterparts, is not intimately linked to intron-encoded maturases.

The canonical amoebot model: algorithms and concurrency control

The amoebot model abstracts active programmable matter as a collection of simple computational elements called amoebots that interact locally to collectively achieve tasks of coordination and movement. Since its introduction at SPAA 2014, a growing body of literature has adapted its assumptions for a variety of problems; however, without a standardized hierarchy of assumptions, precise systematic comparison of results under the amoebot model is difficult. We propose the canonical amoebot model, an updated formalization that distinguishes between core model features and families of assumption variants. A key improvement addressed by the canonical amoebot model is concurrency. Much of the existing literature implicitly assumes amoebot actions are isolated and reliable, reducing analysis to the sequential setting where at most one amoebot is active at a time. However, real programmable matter systems are concurrent. The canonical amoebot model formalizes all amoebot communication as message passing, leveraging adversarial activation models of concurrent executions. Under this granular treatment of time, we take two complementary approaches to concurrent algorithm design. We first establish a set of sufficient conditions for algorithm correctness under any concurrent execution, embedding concurrency control directly in algorithm design. We then present a concurrency control framework that uses locks to convert amoebot algorithms that terminate in the sequential setting and satisfy certain conventions into algorithms that exhibit equivalent behavior in the concurrent setting. As a case study, we demonstrate both approaches using a simple algorithm for hexagon formation. Together, the canonical amoebot model and these complementary approaches to concurrent algorithm design open new directions for distributed computing research on programmable matter.

Text-Mining to Identify Gene Sets Involved in Biocorrosion by Sulfate-Reducing Bacteria: A Semi-Automated Workflow.

A significant amount of literature is available on biocorrosion, which makes manual extraction of crucial information such as genes and proteins a laborious task. Despite the fast growth of biology related corrosion studies, there is a limited number of gene collections relating to the corrosion process (biocorrosion). Text mining offers a potential solution by automatically extracting the essential information from unstructured text. We present a text mining workflow that extracts biocorrosion associated genes/proteins in sulfate-reducing bacteria (SRB) from literature databases (e.g., PubMed and PMC). This semi-automatic workflow is built with the Named Entity Recognition (NER) method and Convolutional Neural Network (CNN) model. With PubMed and PMCID as inputs, the workflow identified 227 genes belonging to several Desulfovibrio species. To validate their functions, Gene Ontology (GO) enrichment and biological network analysis was performed using UniprotKB and STRING-DB, respectively. The GO analysis showed that metal ion binding, sulfur binding, and electron transport were among the principal molecular functions. Furthermore, the biological network analysis generated three interlinked clusters containing genes involved in metal ion binding, cellular respiration, and electron transfer, which suggests the involvement of the extracted gene set in biocorrosion. Finally, the dataset was validated through manual curation, yielding a similar set of genes as our workflow; among these, hysB and hydA, and sat and dsrB were identified as the metal ion binding and sulfur metabolism genes, respectively. The identified genes were mapped with the pangenome of 63 SRB genomes that yielded the distribution of these genes across 63 SRB based on the amino acid sequence similarity and were further categorized as core and accessory gene families. SRB's role in biocorrosion involves the transfer of electrons from the metal surface via a hydrogen medium to the sulfate reduction pathway. Therefore, genes encoding hydrogenases and cytochromes might be participating in removing hydrogen from the metals through electron transfer. Moreover, the production of corrosive sulfide from the sulfur metabolism indirectly contributes to the localized pitting of the metals. After the corroboration of text mining results with SRB biocorrosion mechanisms, we suggest that the text mining framework could be utilized for genes/proteins extraction and significantly reduce the manual curation time.

Scaling the living space: Zipf’s law for traditional courtyard houses in South China

In the traditional feudalistic society of China, there is a characteristic residential pattern of several core families with common ancestors living together in one house, as far as possible. Hence, the habitation of large families and their social dynamic always have a complex function and hierarchical structure. In this article, we consider a courtyard in South China as an example to enable a discussion of the mathematical relationship among the five basic functional spaces in it. Based on Zipf’s law, we find that the distribution of the five types of spaces, from large to small, can be described by the Pareto distribution with a shape parameter close to −1. Moreover, the Zipf parameters of different houses in the same area conform to the double Pareto distribution. This suggests that the size and shape of a residence also follows well-defined scaling laws. Additionally, it indicates that houses, at least traditional Chinese houses, have strong self-organization and self-similarity. It also shows that the power law of the Pareto distribution is applicable not only to the macro scale of the city but also the micro scale of housing.

The role of family counseling in handling autistic children during at-home learning periods

The creation of good relations between family members during the COVID-19 pandemic is considered important to accommodate the learning needs of autistic children as during the pandemic, they are not able to learn optimally. This study aims to establish the role of family counseling in handling autistic children during at-home learning. The research uses a qualitative case study design. The informants were parents and core families of autistic children, and data collection involved interviews, observations, and documentation. The data analysis techniques employed were inductive analysis through reduction, data description, data coding, interpretation, and conclusions. The results show that the involvement of family members took place on a scheduled basis, relations between them improve, and making independent. The passion for building self-potential by developing a sense of respect for family members who help with autistic children's activities when learning from home. Family counseling through the involvement of family members can have a positive effect on the behavioral development of autistic children and a beneficial impact on other family members. The implication is that family counseling can be applied to help the social-emotional development of autistic children.

|tPRiors |: a tool for prior elicitation and obtaining posterior distributions of true disease prevalence

BackgroundTests have false positive or false negative results, which, if not properly accounted for, may provide misleading apparent prevalence estimates based on the observed rate of positive tests and not the true disease prevalence estimates. Methods to estimate the true prevalence of disease, adjusting for the sensitivity and the specificity of the diagnostic tests are available and can be applied, though, such procedures can be cumbersome to researchers with or without a solid statistical background. This manuscript introduces a web-based application that integrates statistical methods for Bayesian inference of true disease prevalence based on prior elicitation for the accuracy of the diagnostic tests. This tool allows practitioners to simultaneously analyse and visualize results while using interactive sliders and output prior/posterior plots.Methods - implementationThree methods for prevalence prior elicitation and four core families of Bayesian methods have been combined and incorporated in this web tool. |tPRiors| user interface has been developed with R and Shiny and may be freely accessed on-line.Results|tPRiors| allows researchers to use preloaded data or upload their own datasets and perform analysis on either single or multiple population groups clusters, allowing, if needed, for excess zero prevalence. The final report is exported in raw parts either as.rdata or.png files and can be further analysed. We utilize a real multiple-population and a toy single-population dataset to demonstrate the robustness and capabilities of |tPRiors|.ConclusionsWe expect |tPRiors| to be helpful for researchers interested in true disease prevalence estimation and who are keen on accounting for prior information. |tPRiors| acts both as a statistical tool and a simplified step-by-step statistical framework that facilitates the use of complex Bayesian methods. The application of |tPRiors| is expected to aid standardization of practices in the field of Bayesian modelling on subject and multiple group-based true prevalence estimation.

Detection of the Core Bacteria in Colostrum and Their Association with the Rectal Microbiota and with Milk Composition in Two Dairy Cow Farms.

Simple SummaryIn order to provide information on developing probiotics for newborn calves, this research detected the bacterial composition in colostrum and rectal feces of healthy Holstein cows from two dairy farms. Our results found several core bacterial species and some core genus and families in colostrum. About half of the OTUs detected in colostrum were found in the rectal content including some strictly anaerobic bacteria. In addition, some well-known intestinal beneficial bacteria including Lactobacillus plantarum and Bacillus subtilis were present in cow colostrum. Our results confirm that colostrum provides intestinal probiotics for calves. Furthermore, we might be able to develop new probiotics for calves according to the core symbiotic genus or families in colostrum.As one of the pioneer bacterial sources of intestinal microbiota, the information of bacterial composition in colostrum might provide a reference for developing specific probiotics for newborn calves, especially calves fed with pasteurized milk. The present study aimed to detect the core bacteria at different taxonomic levels and the common beneficial ones in colostrum by analyzing the bacterial composition in 34 colostrum samples of healthy cows selected from two dairy farms. The results of the further analysis showed that the bacterial composition in the colostrum of the two dairy farms was different, but their four most dominant phyla were the same including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The microbiome of all colostrum samples shared ten core operational taxonomic units (OTUs), 21 core genera, and 34 core families, and most of them had no difference in relative abundance between the two farms. The ten core OTUs did not belong to the identified commensal bacteria and have not been detected by previous study. However, several core genera found in our study were also identified as core genus in a previous study. Some well-known beneficial and pathogenic bacteria including Lactobacillus plantarum, Bacillus subtilis, Acinetobacter lwoffii, and Streptococcus pneumoniae were present in the colostrum of healthy cows. However, none had a correlation with the number of somatic cell count (SCC), but the core genera Nubella and Brevundinimas and the core families Methylobacteriaceae and Caulobacteraceae positively correlated with the number of SCC. The genus Staphylococcus, Pseudomonas, and Chryseobacterium in colostrum had a positive correlation with each other, while the probiotics unidentified-Bacteroidales-S24-7-group had a negative correlation with Pseudomonas and Chryseobacterium. In addition, more than 50% bacterial OTUs in colostrum were detected in the rectal content including some strictly anaerobic bacteria that are generally present in the intestine and rumen. However, of the top 30 commonly shared bacterial genera in the colostrum and rectal feces, no genus in colostrum was positively correlated with that same genus in rectal feces. In conclusion, the bacterial composition of colostrum microbiota is greatly influenced by external factors and individuals. There were several core OTUs, and some core genus and families in the colostrum samples. Colostrum from healthy cows contained both beneficial and pathogenic bacteria and shared many common bacteria with rectal content including some gastrointestinal anaerobes.

Design Flexibility of a Modular Low-Loss High-Frequency Inductor Structure

Miniaturization and efficiency of power electronics are limited by magnetic components, which are difficult to scale to small size and high frequency (HF). Inductor structures using field shaping, quasi-distributed gaps, and modular construction can achieve low loss at HF (3-30 MHz) without litz wire. For widespread adoption though, these structures must be shown to remain effective across a wide design range and be economical to manufacture. This article investigates the design flexibility of one such previously proposed inductor structure with a modified pot core and demonstrates that this structure can provide excellent performance for a wide range of inductance and power handling requirements using only a few sets of manufactured core pieces. The core pieces used in the modified pot core structure can be scaled by 4× in volume, compared to roughly 2× for conventional core families, and still achieve high performance over a wide design space. Moreover, this approach can achieve about half the loss of conventional designs at HF and, unlike conventional core sets, can provide a range of low-loss form factors with a single family of components. The proposed inductor structure and design approaches, thus, offer new opportunities in the practical production of low-loss HF inductors.

Moving beyond family: unequal burden across mental health patients' social networks.

Although the family burden of mental health problems on patients' close relatives was widely acknowledged, little was known about how mental health problems affected the quality of life of other types of social relationships of patients, through what mechanisms, and under what conditions. The study aims to explore the burden on all types of relationships of mental health patients and explain why and when the burden is unequal across different relationships. The association between different types of relationships and the levels of burden was examined with dyadic data of 1178 patient-acquaintance relationships in the United States and random effects multilevel models. Frequency of contacts was tested as a mediator. The severity of mental health problems was tested as a moderator. All types of relationships of patients borne a significant burden. Close relatives including parents, spouses, children, and siblings suffered a greater burden than distant relatives and non-relatives. The unequal burden was partly explained by the frequency of contacts with patients. The burden of close relatives significantly increased when patients' mental health problems were more severe. Mental health patients put a burden on their frequent contacts outside core families, especially when their problems were more severe. Public health policies should attend to the quality of life of mental health patients' all types of acquaintances in the wider society.

Two tSNPs in BRIP1 are associated with breast cancer during TDT analysis.

ObjectivesThis study aimed to investigate and confirm the association between 15 single nucleotide polymorphisms of four susceptibility genes (NBS1, TP53, PTEN, and BRIP1) and the susceptibility of breast cancer.MethodsThe genome DNA was extracted from peripheral blood and tumor tissues from one hundred and seventeen core families. 15 SNPs were detected by PCR. The transmission disequilibrium test (TDT) and the Hardy–Weinberg equilibrium (HWE) are used to verify the association between these SNPs and breast cancer. Further correlation between SNPs and certain pathological features of the tumor, including tumor size, location of lymph nodes, pathologic classification, and the stage and subtype of breast cancer, are analyzed by the chi‐square test and logistic regression analysis.ResultsBased on TDTs, two SNPs of rs7220719 and rs11871753 in BRIP1 showed a significant association with breast cancer, while the other 13 selected SNPs did not. However, further statistical analysis demonstrated no obvious differentiation in the clinical characteristics of breast cancer between 37 patients with rs7220719 and 80 patients with wild types. Similar results were also found for rs11871753.ConclusionsThe data provided the evidence for the association between two SNPs of BRIP1 and breast cancer, but did not affect certain clinical phenotypes.

High-throughput screening reveals novel mutations in spinal muscular atrophy patients

BackgroundSpinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of mutated genes is helpful in diagnosis and treatment for SMA.MethodsEighty-three whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing.ResultsTwenty-two probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. Six SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C > T], c.[271C > T], c.[−39A > G] and g.[70240639G > C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[−41_-40insCTCT], FUT5 SNV c.[1001A > G], and MCCC2 SNV c.[−117A > G] were the 3 most frequent mutations in SMA group (95, 85 and 75%, respectively).ConclusionsWe identified some mutations in both SMN1 and other genes, and c.[271C > T], c.[−41_-40insCTCT], c.[1001A > G] and c.[−117A > G] might be associated with the onset of SMA.

Discovery of specific mutations in spinal muscular atrophy patients by next-generation sequencing.

Spinal muscular atrophy (SMA) is a type of autosomal recessive genetic disease, which seriously threatens the health and lives of children and adolescents. We attempted to find some genes and mutations related to the onset of SMA. Eighty-three whole-blood samples were collected from 28 core families, including 28 probands with clinically suspected SMA (20 SMA patients, 5 non-SMA children, and 3 patients with unknown etiology) and their parents. The multiplex ligation probe amplification (MLPA) was performed for preliminary diagnosis. The high-throughput sequencing technology was used to conduct the whole-exome sequencing analysis. We analyzed the mutations in adjacent genes of SMN1 gene and the unique mutations that only occurred in SMA patients. According to the MLPA results, 20 probands were regarded as experimental group and 5 non-SMA children as control group. A total of 10 mutations were identified in the adjacent genes of SMN1 gene. GUSBP1 g.[69515863G>A], GUSBP1 g.[69515870C>T], and SMA4 g.[69515738C>A] were the top three most frequent sites. SMA4 g.[69515726A>G] and OCLN c.[818G>T] have not been reported in the existing relevant researches. Seventeen point mutations in the DYNC1H1 gene were only recognized in SMA children, and the top two most common mutations were c.[2869-34A>T] and c.[345-89A>G]; c.[7473+105C>T] was the splicing mutation that might change the mRNA splicing site. The mutations of SMA4 g.[69515726A>G], OCLN c.[818G>T], DYNC1H1 c.[2869-34A>T], DYNC1H1 c.[345-89A>G], and DYNC1H1 c.[7473+105C>T] in the adjacent genes of SMN1 gene and other genes might be related to the onset of SMA.

Transmission characteristics of SMN from 227 spinal muscular atrophy core families in China

To define the relationship between the survival motor neuron 1 gene (SMN1) and SMN2, and explore the variability of these two genes within the generations, SMN1 and SMN2 copy numbers were determined for 227 SMA families. The association analysis indicated that there was a negative correlation between the copy number of SMN1 and SMN2 (Spearman = −0.472, P < 0.001) in 227 SMA children and 454 of their parents. The average SMN copies from father and mother in each SMA family were used to represent the copy number in the parent’s generation. Subsequently, SMN transmission analysis showed that the similar distribution trend of SMN1 and SMN2 copy number was not only in the SMA children and their parents’ generation but also in the non-SMA families. Moreover, when the SMN2 copy number was one in the parent’s generation, 75% of their SMA children had type I and 25% of them had type II/III. However, when the SMN2 copies were three in the parent’s generation, all of their SMA children were type II/III. Therefore, the diversity of SMN copies was mostly inherited and the SMN2 copy number in the parent’s generation could predict the disease severity of SMA children to some extent.

Influence of validating the parental origin on the clinical interpretation of fetal copy number variations in 141 core family cases.

BackgroundThe sources and variants types of the copy number variations (CNVs) in prenatal fetal, and the critical role of parental origin on the interpretation of fetal CNVs are unclear.MethodsOne hundred and forty‐one prenatal core families with abnormal CNVs were selected and performed by low‐coverage massively parallel CNV sequencing (CNV‐seq).ResultsThe data showed that 72.3% of fetal CNVs were derived from parents, and 27.7% were new variations. Sixty‐three cases were heterozygous deletion, 70 cases were threefold duplication, six cases were complex deletion and duplication, and two cases were fourfold repeats. That means the rate of heterozygous deletion and duplication was approximate one. In addition, in parental‐derived fetal abnormal CNVs reports, before validating parental origin, 62 CNVs were variants of uncertain significance (VUS), 15 CNVs were likely benign, 20 CNVs were likely pathogenic, and 5 CNVs were pathogenic. However, after validating parental origin, the total clinical significance changed into 12 VUS, 89 likely benign, 1 likely pathogenic, and 0 pathogenic. The clinical interpretation of 78.4% fetal CNVs was changed and tended to be benign after parental CNVs were detected. Besides, we followed up all families. 93.3% parental‐derived fetal and 30.3% fetus in new mutation group were born healthy.ConclusionParental origin verification has an important significance for interpretation on the clinical significance of fetal CNVs.

Correlation between TGF-B gene promoter-509C/T polymorphism and IgA nephropathy in core families in Guangxi Zhuang Autonomous Region and the therapeutic effect of dendrobium

To investigate the correlation between transformation growth factor (TGF- B) polymorphisms and IgA nephropathy and the therapeutic effect of dendrobium on IgA nephropathy. Polymerase chain reaction- restriction fragment length polymorphism (PCR- RFLP) and direct sequencing were used for analysis of 118 patients with IgA nephropathy from core families in Guangxi Zhuang Autonomous Region. The imbalanced transfer of TGF iso1-509 C/T in the affected offsprings was observed by transfer imbalance test and HRR analysis. The TGF-B genotype of the patients and the core family members were detected. The therapeutic effects of Dendrobium candidum combined with hormone and ACEI/ARB treatments were evaluated by observing the patient's urine protein (24 hUpr), serum albumin (ALB), creatinine (Scr) and urea nitrogen (BUN) levels. In the 118 patients with IgA nephropathy, we identified TGF-B 1 promoter -509C/T genotype CC in 32 (27.1%) cases, CT in 58 (49.2%) cases, and TT in 28 (23.7%) cases. In the core family of the patients, CC genotype was found in 33 (28.0%) cases, CT in 55 (46.6%) cases, and TT in 30 (28.0%) cases. The treatments significantly lowered 24 hUpr, Scr, and BUN levels (P > 0.05) in patients with CC genotype, significantly lowered 24 hUpr and BUN levels in patients with CT genotype (P < 0.05), and significantly lowered 24 hUpr and BUN level and increased (P < 0.05) ALB level (P < 0.01) in patients with TT genotype. There is no significant correlation between TGF-B promoter - 509C/T polymorphism and IgA nephropathy. The patients with CC genotype are sensitive to the treatments with hormone and ACEI/ ARB and show a stronger response to combined treatments with dendrobium.