Genetic Research Studies Research Articles

EPID-24. OPTIMIZING PATIENT RECRUITMENT FOR BRAIN TUMOR STUDIES: LEVERAGING THE POWER OF GOOGLE ADS TO CONNECT WITH AFFECTED FAMILIES

Abstract OBJECTIVE We assessed the effectiveness of using Google Ads to recruit individuals with familial glioma into a genetic research study. METHODS We conducted a comparative analysis between two periods: March 1 to June 30, 2023 (with Google Ads) and March 1 to June 30, 2021 (without Google Ads). We targeted individuals searching for brain tumor information using Google Ads, directing them to a study landing page. We analyzed metrics such as advertisement clicks, impressions, click-through rate, and cost per click. Our eligibility criteria included families with at least two members having glioma, with one currently living with the condition, aged 18 or older, and residing in the United States. RESULTS The 2023 Google Ads campaign generated 7,228 clicks, 82,242 impressions, an 8.79% click-through rate, and a cost per click of $0.62. The number of interested individuals increased from 13 in 2021 (without Google Ads) to 35 in 2023 (with Google Ads), with 20 indicating they found the study through Google Ads. However, the increase lacked statistical significance (x2=1.48, p=0.22). CONCLUSION Google Ads enhanced our participant outreach and recruitment for the glioma study, although the results were not statistically significant. This approach shows promise for recruiting participants for rare disease research. We recommend that future studies consider longer durations and larger sample sizes to better assess its impact. Additionally, due to the prevalence of misinformation about familial glioma, we submitted and conducted a survey to the Society of NeuroOncology to evaluate the attitudes and beliefs of physicians and other healthcare professionals towards familial glioma. This survey aims to address misconceptions and improve understanding within the healthcare community.

Identification of genetic risk variants for Type-2 Diabetes mellitus in Pakistani Pashtun population: A case-control association study

Background and Objective: Pakistan, a South Asian developing country, is experiencing a rapid increase in number of diabetes cases. High prevalence ratio of diabetes in Pakistani population and lack of genetic research studies prompted us to design this study. This present study investigated Pakistani Pashtun population for (known and novel SNPs) and its possible correlation with Type-2 Diabetes Mellitus (T2DM). Methods: This two stage (discovery & validation stage), case-control association study included one thousand individuals (Patients with T2DM=500 & controls=500) from eight districts of Khyber Pakhtunkhwa Pakistan. The study duration/period was from March 2018 to January 2020. In the first stage (the discovery stage) the target population was screened for known and novel T2DM-associated genetic markers. In the validation stage, identified variants were confirmed for T2DM association using MassARRAY genotyping and association analysis. Results: Exome sequencing detected eleven known and four novel/new genetic markers in the study population. Novel variants were preferred over the known for follow-up analysis/validation. Among the identified variants strong associations were confirmed for the following variants; rs1781133/ANKRD65 (OR=2.10, 95%Cl=1.06–3.08, P=0.003) rs2274791/TTLL10 (OR=1.97, 95%Cl=1.36-2.62, P=0.025), rs71628928/RNF223 (OR=1.82, 95%Cl=0.97-1.92, P=0.041), and rs609805/SCNN1D (OR=2.21, 95%Cl=1.92-3.09, P=0.001) with T2DM; other reported variants showed no noticeable association (having P>0.05) with T2DM. Conclusion: This study reports new genetic risk variants for T2DM in Pashtun population providing valuable insights into the genetic basis of T2DM in this group. doi: https://doi.org/10.12669/pjms.40.10.10292 How to cite this: Jan A, Mothana RA, Kaimori JY, Muhammad T, Khan M, Ali SS, et al. Identification of genetic risk variants for Type-2 Diabetes mellitus in Pakistani Pashtun population: A case-control association study. Pak J Med Sci. 2024;40(10):2336-2343. doi: https://doi.org/10.12669/pjms.40.10.10292 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract B055: Engaging Black and African American community members to develop culturally appropriate methods for cancer genetics education, risk assessment, and referral to research studies and clinical services: A community café approach

Abstract Background: Patients who have a potentially hereditary cancer (e.g., breast, ovarian, prostate) and self-identify as Black or African American (AA) are less likely to receive cancer genetic services than their White peers. Prior research indicates that the lack of consistent identification and referral of test-eligible patients and their family members is a significant barrier to receiving this care. Additionally, AA patients who do reach these services are much more likely than White patients to receive genetic test results that contain a variant of unknown significance (VUS). This disparity is largely attributable to the lower proportion of non-White patients included in cancer genetic research and clinically derived datasets. Developing culturally appropriate, community-informed, and community-based approaches to improve access to cancer genetic research and clinical care is critical to reducing these disparities. Methods: We used a community and patient engaged research (CPER) framework to develop and implement a series of community cafés. The foundation of the community café model is bi-directional engagement that emphasizes the critical roles of cultural awareness, empathy, and trust in healthcare and research improvement. Accordingly, we developed two brief educational modules that oriented café participants to the topics of 1) genetics and diversity in cancer research and 2) the role of family history in cancer risk assessment. Each ∼10 minute module was followed by a 30-40 minute facilitated listening session, enabling café participants to provide substantial feedback on both topics. Sessions were structured to generate input on the development of training and practice support materials for community health workers (CHWs) in the next phase of this research project. Note takers summarized the discussion at the end of each session, providing café participants an opportunity to revise or elaborate upon the written notes. Café sessions were also audio recorded for future transcription. Results: Eight community cafes were held from January-May 2024. Six cafes consisted of 121 AA community members (75.8% female; mean age = 53.4 years), most of whom had either been diagnosed with cancer (29.8%) or had a first-degree relative with cancer (31.4%). Two cafes enrolled a total of 21 CHWs (90.5% female; mean age = 45.4 years). Several actionable themes emerged during the listening sessions, including: clear explanations regarding why AA patients are being recruited into cancer genetic research studies, acknowledging harms of past race-based research; increased awareness of CHWs and how they can help build trust and bridge gaps between community members and academic medical centers. Café participants strongly endorsed increased presence of clinicians and researchers in community settings and increased representation of Black or African Americans on clinical and research teams. Impact: The community café approach was well received by community members, generating important input into the development of a community-based, equity-focused intervention. Citation Format: Erin Linnenbringer, Briana Wilson, Kayla Wallace, Anjali Kunavarapu, Charles Cogshell, Bailey Martin-Giacalone, Meera Muthukrishnan, Brett Maricque, Jessica Mozersky, Bettina Drake, Joyce Balls-Berry. Engaging Black and African American community members to develop culturally appropriate methods for cancer genetics education, risk assessment, and referral to research studies and clinical services: A community café approach [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B055.

Development of a haplotype reference panel and analysis of genetic structure in Golden Pompano (Trachinotus ovatus)

Trachinotus ovatus, a valuable marine fish, is primarily farmed in the South China Sea. Intensive aquaculture can lead to genetic uniformity and disease risks. Additionally, the high cost of genome sequencing restricts knowledge of genetic variation, hindering genetic analysis and breeding advancements. This study investigated the genetic diversity and structure of Trachinotus ovatus populations within the South China Sea aquaculture context, with the goal of strengthening sustainability. Additionally, the study also enhanced breeding strategies by developing a high-quality haplotype reference panel and an efficient imputation process. Through high-throughput sequencing (depth＞20X), 173 samples from three key breeding sites (SanYa, Hainan; Zhanjiang, Guangdong; and Beihai, Guangxi) were analyzed, revealing substantial genetic diversity and distinct population structures. Notably, the Beihai (BH) population exhibited significant stratification, suggesting regional genetic uniqueness. Low levels of genomic inbreeding coefficient and the identification of unique SNP loci across populations underscored the genetic richness within these Trachinotus ovatus communities. A major constructed of this work is the creation of the first high-quality haplotype reference panel for the species, demonstrating genotype imputation's viability as a cost-effective alternative for large-scale genetic studies in aquaculture. In particular, a Shapeit reference panel with 5476,550 SNPs was created, excelling in accuracy across various depths, notably achieving up to 95.8 % imputation accuracy at 1X sequencing depth. This high accuracy across populations shows the importance of genetic diversity in the panel. This research not only advances the understanding of Trachinotus ovatus genetic foundations but also provides crucial insights for conservation efforts and genetic analysis. By establishing a robust haplotype reference panel for Trachinotus ovatus helps lower the costs of future genetic research and variation studies, this study lays the foundation for sustainable aquaculture practices and breeding programs.

413 Perceptions and Concerns: Navigating Genetic Research Participation Among At-Risk Individuals for Inherited Conditions

OBJECTIVES/GOALS: Motivations and hesitations about participating in genetic research among those at risk of inherited conditions are unclear. We aim to understand perceptions, perspectives, and concerns of these individuals regarding genetic research studies, especially for hard-to-diagnose diseases. METHODS/STUDY POPULATION: Mix method study of 150 Hispanics individuals in Puerto Rico (PR) at risk for in heriting a condition. These individuals, with limited diagnostic data, are attending genetics clinics or invited to a genetics study at the University of Puerto Rico Medical Sciences Campus. Structured surveys and interviews will be conducted. Surveys will gauge general perceptions and feelings toward genetic research, while interviews will provide a deeper understanding of participants’ personal narratives and experiences. All sessions will be recorded, transcribed, and analyzed using NVivo qualitative analysis software. Thematic analysis will be employed to identify recurring themes and sentiments. RESULTS/ANTICIPATED RESULTS: Weanticipatevaried responses: some enthusiastic about genetic research benefits, others having reservations due to privacy, cultural beliefs, or past experiences. A significant portion may express concerns about genetic research’s impact on insurance and potential discrimination. We also expect to uncover systemic challenges that hinder participation among Hispanics living in PR, such as a lack of information or misconceptions about genetic research. This study will overview factors, both encouraging and inhibitory, influencing decisions to join genetic research. Quantitative genetic literacy survey data will undergo descriptive analysis and multivariate logistic regression. DISCUSSION/SIGNIFICANCE: Hispanics in PR exhibit a rich tapestry of genetic variations being a focal point for genetic research. Understanding perceptions is vital among those at risk for inherited conditions. Insights can shape outreach and education strategies, ensuring participants are informed, concerns met, and empowered to make decisions alignined their views.

Genetic Analysis of 27 Y-STR Haplotypes in 11 Iranian Ethnic Groups.

The study of Y-chromosomal variations provides valuable insights into male susceptibility in certain diseases like cardiovascular disease (CVD). In this study, we analyzed paternal lineage in different Iranian ethnic groups, not only to identify developing medical etiology, but also to pave the way for gender-specific targeted strategies and personalized medicine in medical genetic research studies. The diversity of eleven Iranian ethnic groups was studied using 27 Y-chromosomal short tandem repeat (Y-STR) haplotypes from Y-filer® Plus kit. Analysis of molecular variance (AMOVA) based on pair-wise RST along with multidimensional scaling (MDS) calculation and Network phylogenic analysis was employed to quantify the differences between 503 unrelated individuals from each ethnicity. Results from AMOVA calculation confirmed that Gilaks and Azeris showed the largest genetic distance (RST=0.35434); however, Sistanis and Lurs had the smallest considerable genetic distance (RST=0.00483) compared to other ethnicities. Although Azeris had a considerable distance from other ethnicities, they were still close to Turkmens. MDS analysis of ethnic groups gave the indication of lack of similarity between different ethnicities. Besides, network phylogenic analysis demonstrated insignificant clustering between samples. The AMOVA analysis results explain that the close distance of Azeris and Turkmens may be the effect of male-dominant expansions across Central Asia that contributed to historical and demographics of populations in the region. Insignificant differences in network analysis could be the consequence of high mutation events that happened in the Y-STR regions over the years. Considering the ethnic group affiliations in medical research, our results provided an understanding and characterization of Iranian male population for future medical and population genetics studies.

Ethical considerations for genetic research in low-income countries: perceptions of informed consent, data sharing, and expectations in Nicaragua

Genetic research presents numerous ethical, legal, and social implications (ELSI), particularly when the research involves collaborations between investigators in high and low-income countries. Some ELSI issues are universal, and others are specific to context and culture. This study investigates perceptions of genetic research in Nicaragua, Central America, where local and U.S. based researchers have collaborated for over a decade. A total of 43 residents from northwestern Nicaragua, a region with high mortality rates attributed to chronic kidney disease of non-traditional causes (CKDnt), were interviewed, including research participants in ongoing studies (n = 36), health professionals (n = 3), labor leaders (n = 2), and family members of research participants (n = 2). Questions focused on informed consent, data-sharing, and post-study expectations. Audio recordings of interviews conducted in Spanish were transcribed and translated into English. English transcripts were coded and analyzed using NVivo 12 software. The lack of familiarity with terms in the consent form presented a barrier to participant comprehension of key elements of the genetic research study, raising concerns about the validity of informed consent. Research participants often viewed their participation as access to health care. Health professionals emphasized the importance of long-term partnerships between foreign-based researchers and local health institutions. Leaders and family members recommended that they be informed of research studies and allowed the opportunity to consent, as they felt the benefits and risks of research also apply to them. Our findings identified genetic research practices to be improved upon in order to be more responsive to the contextual realities of collaborators living in low-resource settings.

The Development of Plant Genome Sequencing Technology and Its Conservation and Application in Endangered Gymnosperms.

Genome sequencing is widely recognized as a fundamental pillar in genetic research and legal studies of biological phenomena, providing essential insights for genetic investigations and legal analyses of biological events. The field of genome sequencing has experienced significant progress due to rapid improvements in scientific and technological developments. These advancements encompass not only significant improvements in the speed and quality of sequencing but also provide an unparalleled opportunity to explore the subtle complexities of genomes, particularly in the context of rare species. Such a wide range of possibilities has successfully supported the validation of plant gene functions and the refinement of precision breeding methodologies. This expanded scope now includes a comprehensive exploration of the current state and conservation efforts of gymnosperm gene sequencing, offering invaluable insights into their genomic landscapes. This comprehensive review elucidates the trajectory of development and the diverse applications of genome sequencing. It encompasses various domains, including crop breeding, responses to abiotic stress, species evolutionary dynamics, biodiversity, and the unique challenges faced in the conservation and utilization of gymnosperms. It highlights both ongoing challenges and the unveiling of forthcoming developmental trajectories.

New Morphological and Molecular Data on the Southern Ninespine Stickleback, Pungitius platygaster (Gasterosteidae) from Southern Caspian Sea Basin

Being a group of popular model organisms in eco-evolutionary biology, genetic, and genomic research studies, the genus Pungitius with 12 species is the most species-rich genus in the stickleback family Gasterosteidae including the Caspian nine-spine stickleback, Pungitius platygaster (Kessler, 1859), the only known species from southern Caspian Sea basin. Here, the new data based on morphological and molecular characters of the mtDNA COI barcode region, and current distribution range of P. platygaster is presented. These data confirm the validity of P. platygaster among its congeners, being sister clade to P. hellenicus from Greece. Morphologically, it is distinguished from the other congeneric species by complete pelvic girdle, 8−11 dorsal spines, and presence of large lateral scutes. The Caspian nine-spine stickleback is found in several closely placed freshwater and brackish waterbodies in the southern Caspian Sea.

Construction and functional verification of size-reduced plasmids based on TMP resistance gene dfrB10.

Plasmid size is one of the factors affecting transfection efficacy in most of the molecular genetic research studies. One effective approach for reducing plasmid size is to replace relatively large, conventional antibiotic resistance genes with the short-size dfrB10 gene. The successful construct of a series of dfrB10-based tool plasmids and their functional validation, via comparison with original plasmids, suggest that dfrB10 is a potent drug resistance selection marker. The antibiotic trimethoprim offers convenient usage comparable to that of ampicillin or kanamycin. Additionally, fluorescence analysis has demonstrated the compatibility of TMP with protein expression in various host cells. Based on these findings, TMP-dfrB10 could be an alternative choice for future use in molecular genetic research studies that require miniature plasmids to achieve optimal results.

Experience conducting a community-engaged student research project involving an underrepresented community: A reflective essay.

Recruiting racially and ethnically underrepresented participants into genetics research studies has been challenging. While many institutions have taken steps to address the inequity in genetics research, genetic counseling training programs have the chance to inspire students to engage with underrepresented communities through utilizing different research methodologies. These methodologies can help students focus on research projects that increase access to genetics services and improve clinical care. Community-engaged research (CER) presents a pedagogical approach to enhance service-learning opportunities for students. Furthermore, it allows students to develop practical research skills for doing research with the community, rather than on the community. CER is a collaborative community-academic partnership that leads to mutual benefit and outcomes such as inclusion and engagement of the community in research, building trust and relationships, and increasing cultural awareness and exposure. In addition, CER can be used to address research and healthcare inequities by providing opportunities for genetics professionals and trainees to work closely with underrepresented populations. We aim to highlight the opportunities CER provides to students, mentors, and faculty within the context of graduate research in genetic counseling training from the experiences of a student and an educator. In addition, we hope to emphasize the necessity for projects like these to address the gaps in participation of underrepresented patient populations in research and identify areas that are mutually beneficial to improve health outcomes, patient care experiences, access, and service delivery. This reflective essay illustrates the completion of a CER project that was developed in collaboration with community members to address gaps in clinical genetics services in Indigenous healthcare.

Risk perception and intended behavior change after uninformative genetic results for adult-onset hereditary conditions in unselected patients.

Population genetic screening for preventable adult-onset hereditary conditions may improve disease management and morbidity but most individuals will receive uninformative results that do not indicate higher risk for disease. Investigation into subsequent psychosocial health and behaviors is necessary to inform population screening feasibility, effectiveness, and cost considerations. We conducted a prospective survey study of unselected University of Washington Medicine patients enrolled in a genetic research study screening for pathogenic variation in medically important genes. Survey questions adapted from the Feelings About genomiC Testing Results (FACToR) questionnaire and designed to understand perceived disease risk change and planned health behaviors were administered after receipt of results. Overall, 2761 people received uninformative results and 1352 (49%) completed survey items. Respondents averaged 41 years old, 62% were female, and 56% were Non-Hispanic Asian. Results from the FACToR instrument showed mean (SD) scores of 0.92 (1.34), 7.63 (3.95), 1.65 (2.23), and 0.77 (1.50) for negative emotions, positive emotions, uncertainty, and privacy concerns, respectively, suggesting minimal psychosocial harms from genetic screening. Overall, 12.2% and 9.6% of survey respondents believed that their risk of cancer or heart disease, respectively, had changed after receiving their uninformative genetic screening results. Further, 8.5% of respondents planned to make healthcare changes and 9.1% other behavior changes. Future work is needed to assess observed behavior changes attributable to uninformative screening results and if small changes in behavior among this population have large downstream impacts.

Factors that influence a patient's decision to engage in genetic research.

The most challenging step in clinical research studies is patient recruitment. Many research studies do not reach their targets because of participant rejection. The purpose of this study was to assess patient as well as the community knowledge, motivation, and barriers to participate in genetic research. A cross-section study was conducted between September 2018 and February 2020 using face-to-face interviews with candidate patients from outpatient clinics at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Additionally, an online survey was conducted to assess the community's knowledge, motivation and barriers to participate in genetic research studies. In total, 470 patients were interviewed for this study, with 341 being successfully recruited for the face to face interview, and the other patients being refused owing to time constraints. The majority percentage of the respondents were females. The respondents' mean age was 30, and 52.6% reported having a college degree. The survey results from 388 participants illustrated that around 90% of the participants, participated voluntarily due to a good understanding of genetics studies. The majority held positive attitudes toward being part of genetic research, which exceeded the reported motivation score of >75%. The survey indicated that >90% of individuals were willing to participate to acquire therapeutic benefits or to receive continued aftercare. However, 54.6% of survey participants were worried about the side effects and the risks involved in genetic testing. A higher proportion (71.4%) of respondents reported that lack of knowledge about genetic research was one of the barriers to rejecting participation. Respondents reported relatively high motivation and knowledge for participation in genetic research. However, study participants reported "do not know enough about genetic research" and "lack of time during clinic visit" as a barrier for participation in genetic research.

Incorporating multi-stage diagnosis status to mine associations between genetic risk variants and the multi-modality phenotype network in major depressive disorder

Depression (major depressive disorder, MDD) is a common and serious medical illness. Globally, it is estimated that 5% of adults suffer from depression. Recently, imaging genetics receives growing attention and become a powerful strategy for discoverying the associations between genetic variants (e.g., single-nucleotide polymorphisms, SNPs) and multi-modality brain imaging data. However, most of the existing MDD imaging genetic research studies conducted by clinicians usually utilize simple statistical analysis methods and only consider single-modality brain imaging, which are limited in the deeper discovery of the mechanistic understanding of MDD. It is therefore imperative to utilize a powerful and efficient technology to fully explore associations between genetic variants and multi-modality brain imaging. In this study, we developed a novel imaging genetic association framework to mine the multi-modality phenotype network between genetic risk variants and multi-stage diagnosis status. Specifically, the multi-modality phenotype network consists of voxel node features and connectivity edge features from structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI). Thereafter, an association model based on multi-task learning strategy was adopted to fully explore the relationship between the MDD risk SNP and the multi-modality phenotype network. The multi-stage diagnosis status was introduced to further mine the relation among the multiple modalities of different subjects. A multi-modality brain imaging data and genotype data were collected by us from two hospitals. The experimental results not only demonstrate the effectiveness of our proposed method but also identify some consistent and stable brain regions of interest (ROIs) biomarkers from the node and edge features of multi-modality phenotype network. Moreover, four new and potential risk SNPs associated with MDD were discovered.

Long non-coding RNAs: an overview on miRNA sponging and its co-regulation in lung cancer.

Lung cancer is the most devastating cause of death among all cancers worldwide, and non-small cell lung cancer (NSCLC) accounts for 80% of all the lung cancer cases. Beyond common genetic research and epigenomic studies, the extraordinary investigations of non-coding RNAs have provided insights into the molecular basis of cancer. Existing evidence from various cancer models highlights that the regulation of non-coding RNAs is crucial and that their deregulation may be a common reason for the development and progression of cancer, and competition of cancer therapeutics. Non-coding RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are increasingly recognized as potential cancer biomarkers for early detection and application of therapeutic strategies. The miRNAs have gained importance as master regulators of target mRNAs by negatively regulating their expression. The lncRNAs function as both tumor suppressors and oncogenes, and also compete with miRNAs that influence the translational inhibition processes. This review addresses the role of lncRNAs in lung cancer development, highlights their mechanisms of action, and provides an overview of the impact of lncRNAs on lung cancer survival and progression via miRNA sponging. The improved understanding of lung cancer mechanisms has opened opportunities to analyze molecular markers and their potential therapeutics.

Understanding changes in genetic literacy over time and in genetic research participants

As genomic and personalized medicine becomes mainstream, assessing and understanding the public's genetic literacy is paramount. Because genetic research drives innovation and involves much of the public, it is equally important to assess its impact on genetic literacy. We designed a survey to assess genetic literacy in three ways (familiarity, knowledge, and skills) and distributed it to two distinct samples: 2,050 members of the general population and 2,023 individuals currently enrolled in a large-scale genetic research study. Wecompared these data to a similar survey implemented in 2013. The results indicate that familiarity with basic genetic terms in 2021 (M= 5.36 [range 1-7], p<0.001) and knowledge of genetic concepts in 2021 (M= 9.06 [56.6% correct], p= 0.002) are significantly higher compared to 2013 (familiarity: M= 5.08 [range 1-7]; knowledge: M= 8.72 [54.5% correct]). Those currently enrolled in a genetic study were also significantly more familiar with genetic terms (M= 5.79 [range 1-7], p<0.001) and more knowledgeable of genetic concepts (M= 10.57 [66.1% correct], p<0.001), and they scored higher in skills (M= 3.57 [59.5% correct], p<0.001) than the general population (M= 5.36 [range 1-7]; M= 9.06 [56.6% correct]; M= 2.65 [44.2% correct]). The results suggest that genetic literacy is improving over time, with room for improvement. We conclude that educational interventions are needed to ensure familiarity with and comprehension of basic genetic concepts and suggest further exploration of the impact of genetic research participation on genetic literacy to determine mechanisms for potential interventions.

Pathogenesis and potential therapeutic application of stem cells transplantation in Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disorder which is caused due to repetitive CAG or glutamine expression along the coding region of the Huntington gene. This disease results in certain movement abnormalities, affective disturbances, dementia and cognitive impairments. To this date, there is no proper cure for this rare and fatal neurological condition but there have been certain advancements in the field of genetic animal model research studies to elucidate the understanding of the pathogenesis of this condition. Currently, HD follows a certain therapeutic approach which just relieves the symptoms but doesn't cure the underlying cause of the disease. Stem cell therapy can be a breakthrough in developing a potential cure for this condition. In this review, we have discussed the pathogenesis and the efficacy and clinical practicality of the therapeutic application of stem cell transplantation in Huntington's disease. The application of this groundbreaking therapy on genetically altered animal models has been listed and analyzed in brief.

Old Canaan in a New World: Native Americans and the Lost Tribes of Israel

Old Canaan in a New World: Native Americans and the Lost Tribes of Israel

HLA-A∗03:01 is associated with increased risk of fever, chills, and stronger side effects from Pfizer-BioNTech COVID-19 vaccination.

SummaryCOVID-19 vaccines are safe and highly effective, but some individuals experience unpleasant reactions to vaccination. As the majority of adults in the United States have received a COVID-19 vaccine this year, there is an unprecedented opportunity to study the genetics of reactions to vaccination via surveys of individuals who are already part of genetic research studies. Here, we have queried 17,440 participants in the Helix DNA Discovery Project and Healthy Nevada Project about their reactions to COVID-19 vaccination. Our genome-wide association study identifies an association between severe difficulties with daily routine after vaccination and HLA-A∗03:01. This association was statistically significant only for those who received the Pfizer-BioNTech vaccine (BNT162b2; n = 3,694; p = 4.70E−11; OR = 2.07 [95% CI 1.67–2.56]), and showed a smaller effect size in those who received the Moderna vaccine (mRNA-1273; n = 3,610; p = 0.005; OR = 1.32 [95% CI 1.09–1.59]). In Pfizer-BioNTech recipients, HLA-A∗03:01 was associated with a 2-fold increase in risk of self-reported severe difficulties with daily routine following vaccination. The effect was consistent across ages, sexes, and whether the person had previously had a COVID-19 infection. The reactions experienced by HLA-A∗03:01 carriers were driven by associations with chills, fever, fatigue, and generally feeling unwell.

Perspectives on Genetic Research: Results From a Survey of Navajo Community Members.

The Navajo Nation placed a moratorium on genetic research studies in 2002, in part due to concerns about historical distrust, exploitation, limited expertise and resources, and the lack of a genetics policy. Navajo tribal leaders, scientists, and policy experts are exploring the possibility of lifting the moratorium, developing a genetic research policy, and discussing its potential health implications. This study aimed to identify the key concerns, needs, and desires of Navajo people regarding genetic research. We conducted a survey of Navajo individuals to assess knowledge of the moratorium and research, gauge interest in genetic research, and quantify appropriate genetic research topics to understand broad views and concerns. We performed descriptive statistics and tested associations between relevant categorical variables using Chi-square tests. We hypothesized that individuals with more knowledge about the moratorium and health research increased the likelihood of supporting and participating in genetic research. A total of 690 surveys from Navajo respondents were analyzed. Of these, 63% of respondents reported being unaware of the Navajo Nation’s moratorium on genetic research. There were positive associations between those who knew about the moratorium and willingness to donate biospecimens for research under certain conditions, such as community involvement, review and approval by community leaders, research on diseases affecting the community, and support for lifting the moratorium (p-values < 0.001). We found no significant differences between age, gender, religious/spiritual beliefs, or agency affiliation with knowledge levels of genetics and related topics, participation in relation to beliefs, and donation of biospecimens. Interestingly, respondents who resided off the Navajo Nation were positively associated with having knowledge of the moratorium, having heard of discussions of genetics on the Navajo Nation, and the lawsuit filed by the Havasupai Tribe. Most respondents agreed that it was very important to develop a policy that incorporates cultural knowledge (56%), is beneficial (56%), and has data sharing protections (59%) before allowing genetic research on the Navajo Nation. Overall, a large proportion of respondents (46%) were unsure about lifting the moratorium and instead wanted more genetics education to assess its potential implications. The study results can inform the direction of future guidelines and policies.