scholarly journals Allele-specific transcript abundance: A pilot study in healthy centenarians

2019 ◽  
Author(s):  
Lauren C. Tindale ◽  
Nina Thiessen ◽  
Stephen Leach ◽  
Angela R. Brooks-Wilson
Keyword(s):  
Pilot Study ◽  
Healthy Aging ◽  
Complex Disease ◽  
Transcript Abundance ◽  
Common Complex Disease ◽  
Small Pilot Study ◽  
Risk Variants ◽  
Allele Specific ◽  
Disease Associated Genes ◽  
Cell Fractions

AbstractThe genetic basis of healthy aging and longevity remains largely unexplained. One hypothesis as to why long-lived individuals do not appear to have a lower number of common-complex disease variants, is that despite carrying risk variants, they express disease-linked alleles at a lower level than the wild-type alleles. Allele-specific abundance (ASA) is the different transcript abundance of the two haplotypes of a diploid individual. We sequenced the transcriptomes of four healthy centenarians and four mid-life controls. CIBERSORT was used to estimate blood cell fractions: neutrophils were the most abundant source of RNA, followed by CD8+ T cells, resting NK cells, and monocytes. ASA variants were more common in non-coding than coding regions. Centenarians and controls had a comparable distribution of ASA variants by predicted effect, and we did not observe an overall bias in expression towards major or minor alleles. Immune pathways were most highly represented among the gene set that showed ASA. Although we found evidence of ASA in disease-associated genes and transcription factors, we did not observe any differences in the pattern of expression between centenarians and controls in this small pilot study.

scholarly journals Allele-Specific Transcript Abundance: A Pilot Study in Healthy Centenarians

2019 ◽  
Vol 75 (6) ◽  
pp. 1068-1072
Author(s):  
Lauren C Tindale ◽  
Nina Thiessen ◽  
Stephen Leach ◽  
Angela R Brooks-Wilson
Keyword(s):  
Pilot Study ◽  
Healthy Aging ◽  
Complex Disease ◽  
Transcript Abundance ◽  
Common Complex Disease ◽  
Small Pilot Study ◽  
Risk Variants ◽  
Allele Specific ◽  
Disease Associated Genes ◽  
Cell Fractions

Abstract The genetic basis of healthy aging and longevity remains largely unexplained. One hypothesis as to why long-lived individuals do not appear to have a lower number of common-complex disease variants, is that despite carrying risk variants, they express disease-linked alleles at a lower level than the wild-type alleles. Allele-specific abundance (ASA) is the different transcript abundance of the two haplotypes of a diploid individual. We sequenced the transcriptomes of four healthy centenarians and four mid-life controls. CIBERSORT was used to estimate blood cell fractions: neutrophils were the most abundant source of RNA, followed by CD8+ T cells, resting NK cells, and monocytes. ASA variants were more common in noncoding than coding regions. Centenarians and controls had a comparable distribution of ASA variants by predicted effect, and we did not observe an overall bias in expression toward major or minor alleles. Immune pathways were most highly represented among the gene set that showed ASA. Although we found evidence of ASA in disease-associated genes and transcription factors, we did not observe any differences in the pattern of expression between centenarians and controls in this small pilot study.

Predictors of Success Using a mHealth Intervention in Adults with Prediabetes: Results of a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Nestoras Mathioudakis ◽  
Estelle Everett ◽  
Noora Al-Hajri ◽  
Mohammed Abusamaan ◽  
Clare Lee ◽  
...  
Keyword(s):  
Pilot Study ◽  
Intervention Program ◽  
Area Deprivation ◽  
Inverse Association ◽  
Small Pilot Study ◽  
Mhealth Intervention ◽  
Increased Risk ◽  
Metabolic Equivalent Of Task ◽  
Mobile Intervention ◽  
The Difference

BACKGROUND About one-third of American adults have prediabetes and are at increased risk of type 2 diabetes. Mobile health (mHealth) technologies provide a scalable approach to diabetes prevention by encouraging physical activity (PA), weight loss, and adherence to a healthy diet in large numbers of patients. OBJECTIVE To identify factors associated with improvements in PA and glycated hemoglobin (A1c) measures among prediabetic adults who received a mobile intervention program (smartphone app in combination with a digital body weight scale) in a previously completed pilot study. METHODS We conducted a post hoc analysis of a 3-month prospective, single-arm, observational study using the Sweetch™ mHealth intervention among adults with prediabetes. Change in A1C was calculated as the difference between the 3-month and baseline A1C measurements and was categorized as decrease vs. no decrease. PA was evaluated using the total minutes and metabolic equivalent of task (MET)-hours per week. Change in MET-hours/week was categorized as increase vs. no increase. Age, sex, race, education, employment status, area deprivation, smartphone usage attitudes, and PA stage of change were compared between groups by outcomes of change in A1C and change in MET-hour/week. RESULTS A total of 37 adults received the final Sweetch mobile intervention and were included in the analysis. 62% were female and 81% were white, with average age of 57 years. The median [IQR] baseline A1C was 6.0% [5.8, 6.2]. A1C measure at 3-month was decreased in 24 (65%) participants when compared to baseline A1C. There was an inverse association between average MET-hours per week and change in A1C. Among participants whose A1C decreased vs. did not decrease, the MET-hours per week in last 2 weeks of study was 18.7 (8.4) and 15.0 (7.1), respectively (P=0.19), and the change in MET-hours per week was 2.1 (7.1) and 4.1(6.1), respectively (P=0.41). There were otherwise no statistically significant differences in participant factors by A1C and PA outcomes. CONCLUSIONS In this small pilot study, Sweetch mHealth intervention achieved comparable A1C response prediabetic adults with different individual, sociodemographic and anthropometric characteristics. CLINICALTRIAL ClincialTrials.gov NCT02896010; https://clinicaltrials.gov/ct2/show/NCT02896010 (Archived by WebCite at http://www.webcitation.org/6xJYxrgse)

scholarly journals Validating scoring systems for fracture healing in infants and young children: pilot study

2021 ◽  
Author(s):  
Samuel Crompton ◽  
Fabrizio Messina ◽  
Gillian Klafkowski ◽  
Christine Hall ◽  
Amaka C. Offiah
Keyword(s):  
Pilot Study ◽  
Young Children ◽  
Fracture Healing ◽  
Callus Formation ◽  
Femoral Fractures ◽  
Scoring Systems ◽  
Power Calculation ◽  
Small Pilot Study ◽  
Fractures In Children ◽  
Infants And Young Children

Abstract Background Recent studies have analysed birth-related clavicular fractures to propose time frames for healing that could be applied to dating of all fractures in cases of suspected child abuse. Objective To assess differences in healing rates between femoral fractures and birth-related clavicular fractures in infants and young children. Materials and methods A retrospective 5-year pilot study of femoral fractures in children younger than 3 years of age was performed. Anonymised radiographs were independently scored by two radiologists for stages of fracture healing. In cases of reader disagreement, radiographs were independently scored by a third radiologist. Results In total, 74 radiographs (30 children) met the inclusion criteria. Fracture healing evolved over time with subperiosteal new bone formation (SPNBF) appearing first, followed by callus then remodelling. A power calculation for a single proportion, with a level of confidence of 95% and a margin of error of 5%, showed that in a definitive study, 359 radiographs would be required. Conclusion Although the overall pattern of healing is similar, in this small pilot study, the earliest times for SPNBF and callus formation in femoral fractures appeared to lag behind healing of birth-related clavicular fractures. Remodelling appeared earlier than remodelling of clavicular fractures. A power calculation has determined numbers of femoral radiographs (359) required for a definitive study.

scholarly journals Genetic Vectors as a Tool in Association Studies: Definitions and Application for Study of Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-13
Author(s):  
Igor Sandalov ◽  
Leonid Padyukov
Keyword(s):  
Rheumatoid Arthritis ◽  
Complex Disease ◽  
Association Studies ◽  
Healthy Population ◽  
Common Complex Disease ◽  
New Approach ◽  
Functional Studies ◽  
Biological Interpretation ◽  
Genetic Vectors ◽  
Efficient Selection

To identify putative relations between different genetic factors in the human genome in the development of common complex disease, we mapped the genetic data to an ensemble of spin chains and analysed the data as a quantum system. Each SNP is considered as a spin with three states corresponding to possible genotypes. The combined genotype represents a multispin state, described by the product of individual-spin states. Each person is characterized by a single genetic vector (GV) and individuals with identical GVs comprise the GV group. This consolidation of genotypes into GVs provides integration of multiple genetic variants for a single statistical test and excludes ambiguity of biological interpretation known for allele and haplotype associations. We analyzed two independent cohorts, with 2633 rheumatoid arthritis cases and 2108 healthy controls, and data for 6 SNPs from the HTR2A locus plus shared epitope allele. We found that GVs based on selected markers are highly informative and overlap for 98.3% of the healthy population between two cohorts. Interestingly, some of the GV groups contain either only controls or only cases, thus demonstrating extreme susceptibility or protection features. By using this new approach we confirmed previously detected univariate associations and demonstrated the most efficient selection of SNPs for combined analyses for functional studies.

Burden of Common Complex Disease Variants in the Exomes of Two Healthy Centenarian Brothers

Gerontology ◽  
2015 ◽  
Vol 62 (1) ◽  
pp. 58-62 ◽  
Author(s):  
Lauren C. Tindale ◽  
Andy Zeng ◽  
Karla L. Bretherick ◽  
Stephen Leach ◽  
Nina Thiessen ◽  
...  
Keyword(s):  
Complex Disease ◽  
Common Complex Disease ◽  
Healthy Centenarian

scholarly journals OsteoporosAtlas: a human osteoporosis-related gene database

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6778 ◽  
Author(s):  
Xun Wang ◽  
Lihong Diao ◽  
Dezhi Sun ◽  
Dan Wang ◽  
Jiarun Zhu ◽  
...  
Keyword(s):  
Complex Disease ◽  
Treatment Strategies ◽  
Osteoporotic Fractures ◽  
Relevant Information ◽  
Extensive Literature ◽  
Mineral Density ◽  
Common Complex Disease ◽  
Increased Risk ◽  
Prevention And Treatment ◽  
Pathway Analyses

Background Osteoporosis is a common, complex disease of bone with a strong heritable component, characterized by low bone mineral density, microarchitectural deterioration of bone tissue and an increased risk of fracture. Due to limited drug selection for osteoporosis and increasing morbidity, mortality of osteoporotic fractures, osteoporosis has become a major health burden in aging societies. Current researches for identifying specific loci or genes involved in osteoporosis contribute to a greater understanding of the pathogenesis of osteoporosis and the development of better diagnosis, prevention and treatment strategies. However, little is known about how most causal genes work and interact to influence osteoporosis. Therefore, it is greatly significant to collect and analyze the studies involved in osteoporosis-related genes. Unfortunately, the information about all these osteoporosis-related genes is scattered in a large amount of extensive literature. Currently, there is no specialized database for easily accessing relevant information about osteoporosis-related genes and miRNAs. Methods We extracted data from literature abstracts in PubMed by text-mining and manual curation. Moreover, a local MySQL database containing all the data was developed with PHP on a Windows server. Results OsteoporosAtlas (http://biokb.ncpsb.org/osteoporosis/), the first specialized database for easily accessing relevant information such as osteoporosis-related genes and miRNAs, was constructed and served for researchers. OsteoporosAtlas enables users to retrieve, browse and download osteoporosis-related genes and miRNAs. Gene ontology and pathway analyses were integrated into OsteoporosAtlas. It currently includes 617 human encoding genes, 131 human non-coding miRNAs, and 128 functional roles. We think that OsteoporosAtlas will be an important bioinformatics resource to facilitate a better understanding of the pathogenesis of osteoporosis and developing better diagnosis, prevention and treatment strategies.

scholarly journals The Effect of Coaching on Physical Activity and Quality of Life in Children and Adolescents with Cystic Fibrosis: A Quality Improvement Pilot Study

2010 ◽  
Author(s):  
Anne Swisher ◽  
Kathryn Moffett
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Cystic Fibrosis ◽  
Pilot Study ◽  
Children And Adolescents ◽  
Life Questionnaire ◽  
Activity Levels ◽  
Small Pilot Study ◽  
Phone Calls

Purpose: Physical activity is well known to improve or maintain exercise capacity and overall health in patients with cystic fibrosis (CF). However, many patients do not meet recommended guidelines for physical activity. The purpose of this study was to determine if individualized, targeted coaching could improve the levels of physical activity and quality of life in children and adolescents with CF. Subjects: Twelve children with CF, ages 7 to 17, participated in this study.Method: Each participant completed a physical activity questionnaire (PAQ) and a disease-specific quality of life questionnaire (CFQ) at baseline and three months later. The participants were given pedometers and a 10,000 step per day target. Participants also participated in discussions regarding ways to increase physical activity appropriate for their interest, abilities and age. Weekly follow-up phone calls were made to obtain pedometer counts and discuss physical activities performed. Results: Physical activity scores (PAQ) improved in 6 of 12 participants. Quality of life improved in many dimensions of the CFQ, particularly in vitality (3 of 5 improved); emotional (8 of 12 improved) and respiratory (7 of 12 improved). Conclusions: The results of this small pilot study suggest that an individualized coaching approach to physical activity in children and adolescents with CF may improve physical activity levels and improve important aspects of quality of life in some children with CF.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

scholarly journals A red herring in zebrafish genetics: allele-specific gene expression can underlie altered transcript abundance in zebrafish mutants

2021 ◽  
Author(s):  
Richard J White ◽  
Eirinn Mackay ◽  
Stephen W Wilson ◽  
Elisabeth M Busch-Nentwich
Keyword(s):  
Differentially Expressed Genes ◽  
Differentially Expressed Gene ◽  
Transcript Abundance ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Expression ◽  
Genomic Location ◽  
Allele Specific

In model organisms, RNA sequencing is frequently used to assess the effect of genetic mutations on cellular and developmental processes. Typically, animals heterozygous for a mutation are crossed to produce offspring with different genotypes. Resultant embryos are grouped by genotype to compare homozygous mutant embryos to heterozygous and wild-type siblings. Genes that are differentially expressed between the groups are assumed to reveal insights into the pathways affected by the mutation. Here we show that in zebrafish, differentially expressed genes are often overrepresented on the same chromosome as the mutation due to different levels of expression of alleles from different genetic backgrounds. Using an incross of haplotype-resolved wild-type fish, we found evidence of widespread allele-specific expression, which appears as differential expression when comparing embryos homozygous for a region of the genome to their siblings. When analysing mutant transcriptomes, this means that differentially expressed genes on the same chromosome as a mutation of interest may not be caused by that mutation. Typically, the genomic location of a differentially expressed gene is not considered when interpreting its importance with respect to the phenotype. This could lead to pathways being erroneously implicated or overlooked due to the noise of spurious differentially expressed genes on the same chromosome as the mutation. These observations have implications for the interpretation of RNA-seq experiments involving outbred animals and non-inbred model organisms.

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