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1.
Artigo em Inglês | MEDLINE | ID: mdl-38791807

RESUMO

The COVID-19 pandemic produced acute effects on health inequities, yet more enduring impacts in vulnerable populations in rural Appalachia are understudied. This qualitative study included three focus groups with thirty-nine adults (74% female, mean age 52.7 years) to obtain perspectives on the impact of the COVID-19 pandemic on well-being in Martin County, Kentucky, in fall 2022. Grounded Theory was employed using an iterative inductive-deductive approach to capture the lasting effects of the COVID-19 pandemic on health practices and status. Three prominent themes emerged: (1) increased social isolation; (2) household cost of living strains caused by inflation; and (3) higher food prices and diminished food availability causing shifts in food purchasing and consumption. Participants noted that the rising cost of living resulted in residents having to "choose between medication, food and utilities". Increased food prices resulted in residents "stretching" their food, modifying how they grocery shopped, and limiting meat consumption. Persistent food shortages were exacerbated by there being few grocery stores in the county. Lastly, increased social isolation was profoundly articulated as widely impacting mental health, especially among youth. Our findings underscore the ongoing deleterious effects of inflation and food supply chain disruptions in this rural, geographically isolated community, which resulted in difficult spending choices for residents.


Assuntos
COVID-19 , Abastecimento de Alimentos , População Rural , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Feminino , Pessoa de Meia-Idade , Masculino , População Rural/estatística & dados numéricos , Abastecimento de Alimentos/estatística & dados numéricos , Região dos Apalaches , Adulto , Estado Nutricional , Grupos Focais , SARS-CoV-2 , Idoso , Kentucky , Pandemias , Isolamento Social/psicologia
2.
Front Public Health ; 11: 1142478, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124781

RESUMO

Several environmental level factors exacerbate poor health outcomes in rural populations in the United States, such as lack of access to healthy food and locations to be physically active, which support healthy choices at the individual level. Thus, utilizing innovative place-based approaches in rural locations is essential to improve health outcomes. Leveraging community assets, like Cooperative Extension, is a novel strategy for implementing community-driven interventions. This prospective cohort study (n = 152), recruited in 2019 and surveyed again in 2020 and 2021, examined individual level changes in diet and physical activity in one rural Appalachian county. During this time, multiple community-driven interventions were implemented alongside Cooperative Extension and several community partners. Across the three-year study, the cohort indicated increases in other vegetables and water and reductions in fruits and legumes. There were also reductions in less healthy items such as French fries and sugar-sweetened beverages. The cohort also reported being less likely to engage in physical activity. Our findings suggest that key community-driven programs may have indirect effects on dietary and physical activity choices over time. Outcomes from this study are relevant for public health practitioners and community organizations working within rural Appalachian communities to address health-related behaviors.


Assuntos
Dieta , População Rural , Humanos , Adulto , Estados Unidos , Kentucky , Estudos Prospectivos , Exercício Físico , Verduras
3.
Nutrients ; 14(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36145165

RESUMO

Online grocery shopping has expanded rapidly in the U.S., yet little is known about the retailer's perceptions of online grocery services, which can aid in the expansion of services. Furthermore, many barriers to online grocery utilization persist across geographic areas, especially among Supplemental Nutrition Assistance Program (SNAP)-authorized retailers. This study captured perceived barriers and facilitators of online grocery shopping for managers of SNAP-authorized retailers. Qualitative semi-structured interviews were conducted with managers (n = 23) of grocery stores/supermarkets in urban and rural areas across four different states: TN, KY, NC, and NY. Grocery store managers offering online ordering (n = 15) and managers from brick-and-mortar stores without online services (n = 8) participated in the interviews. Three primary themes emerged among managers offering online ordering: (1) order fulfillment challenges, (2) perceived customer barriers, and (3) perceived customer benefits. Among managers at brick-and-mortar locations without online services, four major themes emerged: (1) thoughts on implementing online shopping, (2) COVID-19 pandemic impacts, (3) competition with other stores, and (4) benefits of maintaining brick-and-mortar shopping. This study provides a deeper understanding of retailers' experience and perceptions of online grocery services among stores authorized to accept SNAP benefits. This perspective is necessary to inform policies and enhance the evolving virtual food marketplace for SNAP customers.


Assuntos
COVID-19 , Assistência Alimentar , Comércio , Abastecimento de Alimentos , Humanos , Pandemias , Supermercados
4.
Artigo em Inglês | MEDLINE | ID: mdl-35329193

RESUMO

Research has examined how the entry of grocery stores into neighborhoods influences dietary outcomes, yet limited evidence suggests a direct correlation between opening a store and changes in dietary intake. A factor that might influence individuals' behavior more directly is the closing of a grocery store where residents shop. This study aims to examine how a grocery closure in a rural Appalachian high poverty county is associated with dietary intake. A cohort of n = 152 individuals were recruited to participate in a longitudinal study examining purchasing habits and dietary intake. At time point two, one year later, n = 74 individuals completed the survey via phone. Results indicate those that switched from shopping at a local grocery store to a supercenter significantly increased their dietary intake of fruit (0.2 ± 0.8), fruits and vegetables (1.4 ± 2.7), alcohol (grams) (17.3 ± 54.1), and tomato sauce (0.1 ± 0.3). A local grocery store closure was associated with a change in shopping behavior and dietary intake. Community-level interventions targeting dietary behaviors must account for neighborhood food environment influences, including grocery store availability. Policy aimed at improving food access in rural communities need to consider approaches to improving a variety of food venues with affordable healthy food, while addressing the evolving grocery shopping behaviors of consumers.


Assuntos
População Rural , Supermercados , Comércio , Estudos Transversais , Ingestão de Alimentos , Abastecimento de Alimentos , Frutas , Humanos , Estudos Longitudinais , Obesidade , Verduras
5.
Artigo em Inglês | MEDLINE | ID: mdl-35055688

RESUMO

Online grocery shopping has the potential to improve access to food, particularly among low-income households located in urban food deserts and rural communities. The primary aim of this pilot intervention was to test whether a three-armed online grocery trial improved fruit and vegetable (F&V) purchases. Rural and urban adults across seven counties in Kentucky, Maryland, and North Carolina were recruited to participate in an 8-week intervention in fall 2021. A total of 184 adults were enrolled into the following groups: (1) brick-and-mortar "BM" (control participants only received reminders to submit weekly grocery shopping receipts); (2) online-only with no support "O" (participants received weekly reminders to grocery shop online and to submit itemized receipts); and (3) online shopping with intervention nudges "O+I" (participants received nudges three times per week to grocery shop online, meal ideas, recipes, Facebook group support, and weekly reminders to shop online and to submit itemized receipts). On average, reported food spending on F/V by the O+I participants was USD 6.84 more compared to the BM arm. Online shopping with behavioral nudges and nutrition information shows great promise for helping customers in diverse locations to navigate the increasing presence of online grocery shopping platforms and to improve F&V purchases.


Assuntos
Abastecimento de Alimentos , População Rural , Adulto , Comportamento do Consumidor , Hábitos , Humanos , População Urbana , Verduras
6.
Artigo em Inglês | MEDLINE | ID: mdl-34886518

RESUMO

Rural communities are disproportionally affected by food insecurity, making them vulnerable to the consequences of supply disruptions caused by the COVID-19 pandemic. While access to food was initially diminished due to food supply disruptions, little is known about the mechanisms through which federal emergency assistance programs impacted food access in rural populations. Through a series of five focus groups in spring 2021, we examined the impact of the COVID-19 pandemic on food access in a rural Appalachian community in Kentucky. Data were analyzed using a Grounded Theory Approach. Findings revealed the following four primary themes: food scarcity in grocery stores; expanded federal food assistance; expanded community food resources; and expanded home gardening. Participants provided details regarding the way increased federal assistance, especially expanded benefits within the Supplemental Nutrition Assistance Program, allowed them to purchase greater quantities of nutritious food. This study unveils the specific impacts of the COVID-19 pandemic on one rural population, including the influence of some social determinants of health on food insecurity. Policymakers and stakeholders should recognize the layered protection of multiple federal emergency assistance programs against food insecurity and the potential for long-term population health promotion in rural areas.


Assuntos
COVID-19 , Assistência Alimentar , Região dos Apalaches/epidemiologia , Insegurança Alimentar , Abastecimento de Alimentos , Humanos , Pandemias , Políticas , População Rural , SARS-CoV-2
7.
Nutrients ; 13(7)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206825

RESUMO

Rural communities in Appalachia are displaying increased obesity prevalence, yet traditional interventions have not provided a broad enough impact to improve dietary consumption patterns. Therefore, expanding efforts that address the food environment and incorporate behavioral nudges through community-developed marketing strategies may be a viable mechanism to improve food and beverage choices within this unique population. This study installed shelf-wobblers across n = 5 gas stations in one rural Appalachian county in Kentucky. Smart Snacks were identified from store inventory lists utilizing the CDC Food Service Guideline for Federal Facilities calculator and were categorized into high-protein snacks, low-fat carbohydrate snacks, meal replacement snacks, and no-calorie beverages. NEMS-CS audits were conducted, and monthly sales data was collected at baseline and for six months thereafter for each store location. A difference-in-difference model was used, adjusting for total sales or total mean sales for each Smart Snack model to assess the percentage change within and between stores. Overall, percent change in mean sales and total sales across all stores resulted in a percentage increase of sales of Smart Snack items following wobbler installment. This study provides unique insight into how a community-driven approach to marketing can influence the sale of healthier food and beverage items.


Assuntos
Alimentos , Marketing , Obesidade , População Rural , Região dos Apalaches , Bebidas , Comportamento de Escolha , Comércio , Preferências Alimentares , Abastecimento de Alimentos , Humanos , Kentucky , Lanches
8.
Artigo em Inglês | MEDLINE | ID: mdl-34300097

RESUMO

Obesity is an increasing public health concern in the U.S. and a contributor to chronic illness, with trends revealing a rise in adult obesity and chronic disease rates among the most vulnerable and disadvantaged populations, including those in rural communities. A mixed-methods approach was used to examine perspectives on perceived physical activity barriers, resources, and level of community support. Researchers utilized the socioecological model to examine the multiple domains that support physical activity in rural Appalachia. The present study focuses on baseline data, including a cohort survey to assess physical activity, health status, and barriers to physical activity, and five focus groups with elected community leaders, community residents, members, and key stakeholders to assess perspectives on physical activity barriers and resources within the county. The cohort survey sample (N = 152) reported a median of 6 barriers (range 0-13) to participating in at least 30 min of physical activity daily. The qualitative analysis yielded three overarching themes related to physical activity participation: lack of motivation, physical environment, and cultural barriers. This mixed-methods study revealed the challenges and perceptions among rural residents across the socioecological model when assessing physical inactivity. Findings can be used to tailor future interventions focused on expanding social support, designing infrastructure, and creating policies that promote physical activity.


Assuntos
Exercício Físico , População Rural , Adulto , Região dos Apalaches , Grupos Focais , Humanos , Kentucky
9.
Food Sci Nutr ; 9(6): 3327-3335, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34136197

RESUMO

Ketogenic, gluten-free breads comprised of almond flour, oat bran fiber, or combinations of both were compared. The textural properties, sensory attributes, and consumer acceptance were analyzed on each bread containing 100% almond flour (AF), 66.7% almond flour with 33.3% oat bran fiber (AOB), 66.7% oat bran fiber with 33.3% almond flour (OBA), and 100% oat bran fiber (OB). AF and AOB breads had a more open crumb structure composed of cells between 1-4 mm2. OBA and OB had a significantly dense crumb pattern made up of more cells less than one millimeter squared. Quantitative-descriptive analysis (QDA) and consumer acceptance testing was conducted 24 hr after baking and mechanical endpoints were evaluated 24, 72, and 120 hr after baking. AF and AOB breads were preferred over OBA and OB breads in QDA evaluation and consumer acceptance scores. Greater percentages of oat bran fiber resulted in a bread that was less moist, firmer in texture, and chewier with trained panelists. In both sensory evaluations, higher amounts of almond flour resulted in higher values in eggy flavor while increased amounts of oat bran fiber correlated with higher values in earthy flavor. Mechanical testing identified higher percentages of almond flour resulted in bread that was less firm and less chewy. Over time, all variations with almond flour became softer and less chewy, while the OB bread increased in firmness. Sensory cohesiveness did not correlate with the mechanical equivalent, identifying a need to re-evaluate the parameters used to calculate this objective endpoint.

10.
Prev Med Rep ; 24: 101642, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34976693

RESUMO

Sugar-sweetened beverage (SSB) consumption is decreasing nationally, yet intakes remain high in certain sub-populations as new varieties of SSBs are introduced. This study aims to expand on SSB intake patterns among adults living in Appalachia to develop policy, systems, and environmental (PSE) interventions to reduce consumption. Baseline cohort surveys were conducted to examine beverage consumption patterns of adults in one rural Appalachian county in Kentucky using a validated BEVQ-15 instrument. Ages were collapsed into three generational groups - Millennials (22-38 years), Generation X (39-54 years), and Boomers/Silents (≥55 years). Over half (n = 81; 54%) of the sample (n = 150) were Boomers/Silents. Age was a significant predictor of SSB consumption, with Millennials drinking more daily calories of SSB compared to older adults (329.2 kcal v 157.0 kcal v 134.6 kcal, p = 0.05); a significant amount of those calories coming from non-soda SSBs. Millennials were twice as likely to drink sweetened fruit juice drinks (p = 0.0002) and energy drinks (p = 0.01) daily and consumed six times more daily calories from sweetened fruit juice drinks than the other groups (73.5 kcal v 11.1 kcal v 8.0 kcal, p < 0.01). To our knowledge, this is the first study to show beverage choices and consumption patterns in Appalachian adults vary by age and non-soda SSBs are significant sources of added sugar. These findings inform PSE interventions for reducing SSB consumption, such as tailored marketing approaches and technology-based strategies, within a unique setting, and offer insight for nutrition educators and public health professionals working within rural, remote communities.

11.
Prev Chronic Dis ; 17: E165, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357305

RESUMO

INTRODUCTION: Obesity disproportionately affects rural communities, and Appalachia has some of the highest obesity rates in the nation. Successful policy, systems, and environmental (PSE) interventions to reduce obesity must reflect the circumstances of the population. We used a health equity lens to identify barriers and facilitators for healthy food access in Martin County, Kentucky, to design interventions responsive to social, cultural, and historical contexts. METHODS: We conducted 5 focus groups in Martin County, Kentucky, in fall 2019 to obtain perspectives on the local food system and gauge acceptability of PSE interventions. We used grounded theory to identify perceived barriers and facilitators for healthy eating. RESULTS: Thirty-four adults (27 women; median age, 46 years) participated in 5 groups. One prominent theme was declining interest in farming; many participants believed this decline was generational. One participant noted, "Most of my adult male relatives worked in the coal mines, and they worked 6 days a week. . . . My grandpa had the garden, but then my dad's generation is the one quit gardening." Another shared, "You would probably have to have someone to teach [gardening]." Instead of enhancing farmers markets, participants suggested building community capacity for home gardens to increase vegetable consumption. CONCLUSION: Our findings demonstrate the importance of obtaining community input on the development of PSE interventions to mitigate inequities in obesity. Although farmers market interventions were deemed not feasible, other solutions to enhance access to produce were identified. Developers of community-responsive PSE interventions to improve healthy eating in rural, food-insecure locations should consider using an equity-oriented prevention framework to ensure acceptable interventions.


Assuntos
Dieta Saudável , População Rural , Região dos Apalaches , Feminino , Abastecimento de Alimentos , Jardinagem , Humanos , Masculino , Pessoa de Meia-Idade , Verduras
12.
Artigo em Inglês | MEDLINE | ID: mdl-32825144

RESUMO

The burden of obesity disproportionately influences poor health outcomes in rural communities in the United States. Various social and environmental factors contribute to inadequate food access and availability in rural areas, influencing dietary intakes and food insecurity rates. This study aims to identify patterns related to food insecurity and fruit and vegetable consumption within a SNAP-eligible and low-income, highly obese rural Appalachian community. A prospective cohort was implemented to identify gaps in resources addressing obesity and food insecurity challenges. SAS 9.4 software was used to examine differences in dietary intakes and shopping practices among SNAP participants. Among participants (n = 152), most reported an annual household income less than USD 20,000 (n = 90, 60.4%), 29.1% reported food insecurity, and 39.5% reported receiving SNAP benefits within the last month. The overall mean FV intake was 3.46 daily servings (95% CI: 3.06-3.91) among all participants. SNAP participation was associated with food insecurity (p = 0.007) and those participating in SNAP were two times more likely to report being food insecure (OR = 2.707, 95% CI: 1.317, 5.563), relative to non-participants. These findings further depict the need for intervention, as the burden of food insecurity persists. Tailoring health-promoting initiatives to consider rurality and SNAP participation is vital for sustainable success among these populations.


Assuntos
Assistência Alimentar , Insegurança Alimentar , População Rural , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dieta , Feminino , Abastecimento de Alimentos , Necessidades e Demandas de Serviços de Saúde , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Pobreza , Estudos Prospectivos , Características de Residência , Estados Unidos , Adulto Jovem
13.
Muscle Nerve ; 59(1): 10-22, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29979464

RESUMO

Amyotrophic lateral sclerosis (ALS) is a severely debilitating disease characterized by progressive degeneration of motor neurons. Charcot first described ALS in 18691 ; however, its pathogenesis remains unknown, and effective treatments remain elusive. It is apparent that new paradigms must be investigated to understand the effectors of ALS, including inflammation, immune responses, and the body's response to stress and injury. Herein we discuss the potential role of the immune system in ALS pathogenesis and critically review evidence from patient and animal studies. Although immune system components may indeed play a role in ALS pathogenesis, studies implicating immune cells, antibodies, and cytokines in early disease pathology are limited. We propose more focused studies that examine the role of the immune system together with characterized pathogenesis to determine when, where, and if immune and inflammatory processes are critical to disease progression, and thus worthy targets of intervention. Muscle Nerve 59:10-22, 2019.


Assuntos
Esclerose Lateral Amiotrófica , Imunidade , Inflamação/complicações , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/etiologia , Esclerose Lateral Amiotrófica/imunologia , Esclerose Lateral Amiotrófica/patologia , Animais , Humanos
14.
Mol Microbiol ; 110(6): 897-913, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29802781

RESUMO

Bacterial biofilms are communities of microbial cells encased within a self-produced polymeric matrix. In the Bacillus subtilis biofilm matrix, the extracellular fibres of TasA are essential. Here, a recombinant expression system allows interrogation of TasA, revealing that monomeric and fibre forms of TasA have identical secondary structure, suggesting that fibrous TasA is a linear assembly of globular units. Recombinant TasA fibres form spontaneously, and share the biological activity of TasA fibres extracted from B. subtilis, whereas a TasA variant restricted to a monomeric form is inactive and subjected to extracellular proteolysis. The biophysical properties of both native and recombinant TasA fibres indicate that they are not functional amyloid-like fibres. A gel formed by TasA fibres can recover after physical shear force, suggesting that the biofilm matrix is not static and that these properties may enable B. subtilis to remodel its local environment in response to external cues. Using recombinant fibres formed by TasA orthologues we uncover species variability in the ability of heterologous fibres to cross-complement the B. subtilis tasA deletion. These findings are indicative of specificity in the biophysical requirements of the TasA fibres across different species and/or reflect the precise molecular interactions needed for biofilm matrix assembly.


Assuntos
Proteínas Amiloidogênicas/metabolismo , Bacillus subtilis/fisiologia , Proteínas de Bactérias/metabolismo , Biofilmes , Proteínas Amiloidogênicas/química , Proteínas Amiloidogênicas/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-29065444

RESUMO

Background: Obesity rates are higher among rural versus urban adolescents. To examine possible mechanisms for the rural-urban adolescent obesity disparity, we examined the direct and indirect effects of food purchasing patterns, and the home, school, and consumer food environments on dietary intake among rural adolescents. Methods: A baseline survey was conducted among adolescents in eight rural high schools (four in Eastern Kentucky, and four in Eastern North Carolina). Participants answered questions about food purchasing patterns, dietary intake, home food availability, and demographics. The school and consumer food environments were assessed using validated measures from the School Meals Cost Study (United States Department of Agriculture-Mathematica) and the Nutrition Environment Measurement Survey for Stores, Restaurants, and Corner Stores. Results: Of 432 adolescents, 55% were normal weight, 24% were overweight, and 21% were obese. There was a direct association between unhealthy food purchasing patterns (shopping frequently at gas stations, fast food, and dollar stores) and consuming more added sugars, when compared to those with a healthy shopping pattern (shopping less frequently at gas stations, fast food, and dollar stores) [Odds Ratio = 2.41 (95% CI (confidence interval) 0.99, 3.82)]. Those who reported always having fruits and vegetables in the home consumed more servings of fruits and vegetables [OR = 0.31 cups (95% CI 0.22, 0.44)] compared to those who reported never having fruits and vegetables in the home. Adolescents attending a school with a low healthy food availability score consumed fewer servings of fruits and vegetables [-0.001 (95% CI -0.001, 0.0001)] compared to those attending a school with a high healthy food availability score. Conclusions: There are direct associations between food purchasing patterns, the home and school food environments, and dietary intake among rural adolescents. These cross-sectional results informed the development of the "Go Big and Bring it Home" program, a text messaging intervention to improve adolescents' fruit, vegetable, and healthy beverage intake.


Assuntos
Comportamento do Consumidor , Comportamento Alimentar , Promoção da Saúde , População Rural , Adolescente , Saúde do Adolescente , Bebidas , Dieta , Feminino , Frutas , Humanos , Kentucky/epidemiologia , Masculino , North Carolina/epidemiologia , Inquéritos Nutricionais , Sobrepeso/epidemiologia , Instituições Acadêmicas , Verduras
16.
Sci Rep ; 7(1): 6730, 2017 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-28751732

RESUMO

BslA is a protein secreted by Bacillus subtilis which forms a hydrophobic film that coats the biofilm surface and renders it water-repellent. We have characterised three orthologues of BslA from Bacillus amyloliquefaciens, Bacillus licheniformis and Bacillus pumilus as well as a paralogue from B. subtilis called YweA. We find that the three orthologous proteins can substitute for BslA in B. subtilis and confer a degree of protection, whereas YweA cannot. The degree to which the proteins functionally substitute for native BslA correlates with their in vitro biophysical properties. Our results demonstrate the use of naturally-evolved variants to provide a framework for teasing out the molecular basis of interfacial self-assembly.


Assuntos
Bacillus amyloliquefaciens/genética , Bacillus licheniformis/genética , Bacillus pumilus/genética , Bacillus subtilis/genética , Proteínas de Bactérias/química , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Sequência de Aminoácidos , Bacillus amyloliquefaciens/metabolismo , Bacillus licheniformis/metabolismo , Bacillus pumilus/metabolismo , Bacillus subtilis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Clonagem Molecular , Elasticidade , Escherichia coli/genética , Escherichia coli/metabolismo , Teste de Complementação Genética , Variação Genética , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Fenótipo , Filogenia , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
18.
Orphanet J Rare Dis ; 11(1): 125, 2016 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-27628848

RESUMO

BACKGROUND: Although the majority of small in-frame insertions/deletions (indels) has no/little affect on protein function, a small subset of these changes has been causally associated with genetic disorders. Notably, the molecular mechanisms and frequency by which they give rise to disease phenotypes remain largely unknown. The aim of this study is to provide insights into the role of in-frame indels (≤21 nucleotides) in two genetically heterogeneous eye disorders. RESULTS: One hundred eighty-one probands with childhood cataracts and 486 probands with retinal dystrophy underwent multigene panel testing in a clinical diagnostic laboratory. In-frame indels were collected and evaluated both clinically and in silico. Variants that could be modeled in the context of protein structure were identified and analysed using integrative structural modeling. Overall, 55 small in-frame indels were detected in 112 of 667 probands (16.8 %); 17 of these changes were novel to this study and 18 variants were reported clinically. A reliable model of the corresponding protein sequence could be generated for 8 variants. Structural modeling indicated a diverse range of molecular mechanisms of disease including disruption of secondary and tertiary protein structure and alteration of protein-DNA binding sites. CONCLUSIONS: In childhood cataract and retinal dystrophy subjects, one small in-frame indel is clinically reported in every ~37 individuals tested. The clinical utility of computational tools evaluating these changes increases when the full complexity of the involved molecular mechanisms is embraced.


Assuntos
Oftalmopatias/genética , Mutação INDEL/genética , Fases de Leitura/genética , Catarata/genética , Biologia Computacional , Humanos , Distrofias Retinianas/genética
19.
J Med Genet ; 53(11): 761-767, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27208204

RESUMO

BACKGROUND: Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous set of disorders, for which diagnostic second-generation sequencing (next-generation sequencing, NGS) services have been developed worldwide. METHODS: We present the molecular findings of 537 individuals referred to a 105-gene diagnostic NGS test for IRDs. We assess the diagnostic yield, the spectrum of clinical referrals, the variant analysis burden and the genetic heterogeneity of IRD. We retrospectively analyse disease-causing variants, including an assessment of variant frequency in Exome Aggregation Consortium (ExAC). RESULTS: Individuals were referred from 10 clinically distinct classifications of IRD. Of the 4542 variants clinically analysed, we have reported 402 mutations as a cause or a potential cause of disease in 62 of the 105 genes surveyed. These variants account or likely account for the clinical diagnosis of IRD in 51% of the 537 referred individuals. 144 potentially disease-causing mutations were identified as novel at the time of clinical analysis, and we further demonstrate the segregation of known disease-causing variants among individuals with IRD. We show that clinically analysed variants indicated as rare in dbSNP and the Exome Variant Server remain rare in ExAC, and that genes discovered as a cause of IRD in the post-NGS era are rare causes of IRD in a population of clinically surveyed individuals. CONCLUSIONS: Our findings illustrate the continued powerful utility of custom-gene panel diagnostic NGS tests for IRD in the clinic, but suggest clear future avenues for increasing diagnostic yields.

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