Search or ask a question

Why is there a need for variation and polymorphism understanding in the human pangenome?

De Bruijn graph

Human genetic variation

Best insight from top research papers

Understanding variation and polymorphism in the human pangenome is crucial for several reasons. Firstly, the current human reference genome is limited in its representation of global genomic variation, containing biases and errors . A more accurate and diverse representation of variation is needed to improve gene-disease association studies across populations and expand the scope of genomics research . Secondly, pangenome graphs, which incorporate population diversity, have been introduced to overcome the limitations of a single reference genome . These graphs provide a more comprehensive representation of genomic diversity and can be used in a wide range of genomic analyses . Lastly, the development of a human pangenome reference, consisting of multiple genomes capturing maximal variation, will enable a realistic and reliable estimation of the clinical significance of specific variations . This will enhance our understanding of the impact of genetic variations in different populations and improve precision medicine .

Answers from top 4 papers

PDF

Open Access

More filters

Papers (4)	Insight
Open access•Journal Article•DOI From the reference human genome to human pangenome: Premise, promise and challenge Vipin Kumar Singh Vipin Kumar Singh, Shweta Pandey, Anshumouli Bhardwaj - Show less +2 more 10 Nov 2022-Frontiers in Genetics 2 Citations	The paper discusses the need for understanding variation and polymorphism in the human pangenome to develop a more accurate and global representation of genomic variations.
Open access•Posted Content•DOI Construction and representation of human pangenome graphs F. Andreace, Pierre Lechat, Yoann Dufresne, Rayan Chikhi - Show less +3 more 03 Jun 2023-bioRxiv	The provided paper does not directly address the need for variation and polymorphism understanding in the human pangenome.
Open access•Posted Content•DOI ODGI: understanding pangenome graphs Andrea Guarracino, Simon Heumos, Sven Nahnsen, Pjotr Prins, Erik Garrison - Show less +4 more 11 Nov 2021-bioRxiv 14 Citations	The provided paper does not directly address the need for variation and polymorphism understanding in the human pangenome. The paper focuses on the development of ODGI, a suite of tools for analyzing pangenome graphs.
Open access•Journal Article•DOI The Human Pangenome Project: a global resource to map genomic diversity Ting Wang, L. L. Antonacci-Fulton, Kerstin Howe, Heather A. Lawson, Julian K. Lucas, Adam M. Phillippy, Alice B. Popejoy, Mobin Asri, Caryn Nicole Carson, Mark Chaisson, Xian Chang, Robert Cook-Deegan, Adam Felsenfeld, Robert S. Fulton, Erik Garrison, Nanibaa’ A. Garrison, Tina A. Graves-Lindsay, Hanlee P. Ji, Eimear E. Kenny, Barbara A. Koenig, Daofeng Li, Tobias Marschall, Joshua F. McMichael, Adam M. Novak, Deepak Purushotham, Valerie A. Schneider, Baergen I. Schultz, M. Smith, Heidi J. Sofia, Tsachy Weissman, Paul Flicek, Heng Li, Karen H. Miga, Benedict Paten, Erich D. Jarvis, Ira M. Hall, Evan E. Eichler, David Haussler - Show less +37 more 01 Apr 2022-Visual education 124 Citations	The paper does not explicitly mention the need for variation and polymorphism understanding in the human pangenome. The paper primarily focuses on the creation of a more sophisticated and complete human reference genome with a graph-based representation of global genomic diversity. It aims to improve data representation, streamline analyses, and expand the scope of genomics research.

My columns

Related Questions

How does pangenomics help with plant breeding?4 answersPangenomics plays a crucial role in plant breeding by providing a comprehensive understanding of genetic diversity and valuable traits present in crop wild relatives (CWRs). It enables the identification of genomic regions absent in cultivated plants, offering a rich source of traits for breeding endeavors. By utilizing pangenes, which represent all known syntenic orthologues for a gene model, breeders can refine gene annotations in new cultivars, enhancing the quality of gene sets. Pangenomic studies reveal unique sequences related to biological adaptability and important traits, aiding in the selection of desirable characteristics for breeding purposes. The approach of using long-read assemblies in pangenomics facilitates the detection of structural variations and improves variant calling accuracy, essential for understanding disease resistance loci and shaping breeding strategies in crops like melon. Overall, pangenomics accelerates crop improvement through a detailed exploration of genetic variations and heritability.

What is a genetic variation?4 answersGenetic variation refers to the differences in the genetic makeup of individuals within a population or among different populations. These variations can occur at different levels, including the chromosomal, protein, or DNA sequence level. Genetic variations play significant roles in medical research and have implications for disease risk, drug efficacy, and adverse events. They can also affect the health and wellbeing of an individual, including the composition and heterogeneity of microbiota. Genetic variations can be beneficial, such as increasing bone density or developing resistance to malaria, but they can also be associated with diseases like cancer and genetic disorders. Understanding genetic variations is crucial for studying population history, structure, and evolution, as well as for personalized medicine and therapeutic approaches.

How the genomic variations could affect the genes?5 answersGenomic variations can affect genes through various mechanisms. One mechanism is the presence of trans-acting variants, which are DNA variants located on different chromosomes from the genes they affect. These variants can alter gene expression and contribute to phenotypic variation. Another mechanism is structural genomic rearrangements, such as deletions, duplications, and inversions, which can lead to changes in gene copy number and contribute to genomic diversity. Additionally, regulatory variants in non-coding regions of the genome can affect gene expression by influencing promoter usage and enhancer activity. Furthermore, variants in microRNA binding regions can disrupt the normal regulation of mRNA gene expression, leading to cascading biological effects. Overall, these findings highlight the diverse ways in which genomic variations can impact gene expression and contribute to the variability of complex traits and diseases.

What is the importance of allele balance on variants?5 answersAllele balance is important for understanding genetic phenomena such as polyploidy and heterokaryosis, as well as for accurate variant calling in clinical applications. It has been used to infer polyploidy and heterokaryosis in diverse organisms, and can detect departures from a diploid state, including polyploidy, heterokaryosis, a mixed sample, or chromosomal copy number variation. Understanding allele balance biases can help increase the precision of clinical next-generation sequencing (NGS) applications and detect false positive variant calls. Additionally, allele balance can provide insight into the clonal architecture of tumors and the cooperative dynamics between germline and somatic mutations. Furthermore, allele balance analysis in tumors can identify genes and variants that are relevant to carcinogenesis.

What are the specific genotypes that have been reported in cancers?5 answersSpecific genotypes reported in cancers include allele specific copy number alterations, single nucleotide polymorphisms (SNPs), allelic imbalance somatic events, SNPs located in protein coding genes and nearby regulatory regions, and germline variants (SNPs) that interact with somatic mutations. These genotypes have been studied in various tumor types and have been associated with different aspects of cancer biology, such as tumor evolution, risk of developing tumors, prognostic role, predictive role for treatment efficacy/toxicity, and heritability of cancer. The studies highlight the importance of understanding the role of specific genotypes in cancer development and progression, as well as their potential implications for personalized medicine and early detection strategies.

What are genetic polymorphisms?5 answersGenetic polymorphisms are variations in DNA sequences that occur in a population with a frequency of 1% or higher. These variations can be in the form of single nucleotide polymorphisms (SNPs), variable number tandem repeats (VNTRs), or other repetitive DNA sequences. Polymorphisms can be analyzed using techniques such as polymerase chain reaction (PCR), DNA sequencing, fluorescence in situ hybridization, and DNA microarrays. Genetic polymorphisms play a significant role in disease development, drug response, susceptibility to environmental factors, and cancer. They are also used as genetic markers for studying human genome and personalized medicine. Understanding genetic polymorphisms, especially SNPs, can help in understanding the genetics of human phenotype variation and complex human diseases. Various methods such as allele-specific PCR, restriction fragment length polymorphism, microarray technique, and whole genome sequencing can be used to detect genetic polymorphisms.

See what other people are reading

How do social norms and attitudes towards technology impact the adoption rates of new technologies in residential areas?

Social norms and attitudes play a significant role in influencing the adoption rates of new technologies in residential areas. Research indicates that social norms, prices, and psychological factors all affect adoption decisions, with some households welcoming new technologies while others face social pressure and inconvenience, resulting in negative welfare. Additionally, socio-cultural attitudes and practices heavily influence the acceptance of domestic solar energy interventions among low-income urban dwellers, highlighting the importance of considering underlying socio-cultural causes in adoption processes. Furthermore, individual attitudes towards technology are shaped by cognitive dissonance, conformity with peers, and external authority, impacting adoption decisions and the spread of innovations in society. Understanding these dynamics is crucial for designing effective policies to promote the adoption of new technologies in residential areas.What is open source collaboration in software development?

Open source collaboration in software development refers to the cooperative efforts of developers working on interdependent modules to create a cohesive whole within an open source software ecosystem. This collaboration involves sharing tasks, discussing, and completing them, as seen in orgsOSS projects. Developers collaborate on various project files, with test files showing the highest degree of collaboration, possibly due to the critical nature of functionality tests. In open source software ecosystems, developers from different projects collaborate to fix cross-project bugs, with distinct responsibilities allocated between upstream and downstream members, such as problem-finders and decision-makers. The decentralized nature of open source software development allows for large-scale collaborative work, enabling the study of evolving dependencies, developer networks, and success dynamics over time within the ecosystem.Why and how the renewable energy strategies develop in many countries in recent years?

Renewable energy strategies have developed in many countries due to the need for sustainable solutions to energy crises and environmental issues. Policies play a crucial role in encouraging the transition to renewable energy sources, especially with the increasing demand and limitations of conventional energy sources. Factors influencing renewable energy development include industrial infrastructure investment, R&D, financial development, and reducing fossil-based energy consumption. To make renewable energy competitive, countries are studying and implementing massive energy incentive policies, such as tariff incentives, tailored to their potential, technological readiness, and economic conditions. The distribution of energy sources in the past, GDP per capita, energy supply concentration, and costs of fossil fuel consumption relative to GDP also significantly impact the development of renewable energy strategies in countries.How does the integration of generative artificial intelligence impact the effectiveness of adaptive learning systems in professional training?

The integration of generative artificial intelligence (AI) significantly impacts the effectiveness of adaptive learning systems in professional training. Generative AI, such as ChatGPT, has been shown to enhance productivity and output quality in midlevel professional writing tasks, reducing inequality among workers. Additionally, adaptive learning systems, which dynamically adjust to individual learners' needs, have been found to increase engagement, motivation, and self-directed learning among students, while reducing teachers' workloads through timely feedback delivery. The combination of generative AI and adaptive learning technologies can lead to more efficient and engaging professional training experiences, benefiting both learners and educators by leveraging AI advancements to optimize learning outcomes and streamline educational processes.How does impact of social media on mental health?

The impact of social media on mental health is multifaceted. Social media can enhance connection, increase self-esteem, and improve a sense of belonging. However, research consistently shows a correlation between social media use and heightened levels of anxiety, depression, and loneliness. Factors contributing to this negative impact include the comparison trap, cyberbullying, and the constant stream of information. Excessive social media use may lead to negative outcomes like anxiety, depression, and social isolation. Strategies to promote digital well-being and mitigate these effects include fostering healthy online behaviors and positive engagement. Understanding the risks and benefits of social media use, along with promoting mindful consumption, is crucial for maintaining positive mental health outcomes in the digital age.What cell lines are mostly described in literature in OECT applications?

In the realm of Organic Electrochemical Transistor (OECT) applications, particularly in cell impedance sensing, the literature predominantly describes the use of epithelial cells. Specifically, the tightly packed colorectal adenocarcinoma cell line caco-2 and a novel leaky nasopharyngeal carcinoma cell line NPC43 have been highlighted for their sensitivity in cell-based measurement when interfaced with OECTs. These cell lines are chosen due to their distinct barrier integrity properties, which are crucial for assessing physiological functions in multicellular organisms through OECT technology. While the focus on caco-2 and NPC43 cell lines in OECT applications is evident, it's important to note that the broader literature on cell lines in biomedical research encompasses a wide array of cell types. For instance, HEK293, HEK293T, and HeLa cell lines are among the most frequently used in biomedical research, dominating the landscape of in vitro cell culture practices. However, these commonly used cell lines are not specifically mentioned in the context of OECT applications, suggesting a more targeted selection of cell lines based on the specific requirements of OECT technology, such as the need to measure changes in impedance related to barrier integrity. Moreover, the development of cell culture ontologies and databases, as discussed in other contexts, supports the standardized description and annotation of cell lines, including those used in OECT applications. This standardization aids in the comprehensive understanding and evaluation of cell lines across various research domains, including their use in OECTs. In summary, while the broader biomedical research field utilizes a diverse range of cell lines, OECT applications specifically described in the literature focus on epithelial cells like caco-2 and NPC43 due to their relevance in assessing barrier integrity, a key physiological function of interest in OECT studies.How does impact social media on mental health?

Social media's impact on mental health is multifaceted. While it can enhance connections, self-esteem, and belonging, it also correlates with heightened levels of anxiety, depression, and loneliness. The exponential rise in social media users, projected to reach almost 6 billion by 2027, has been accelerated by the COVID-19 pandemic. Research on Thai teenagers shows that excessive social media use can lead to negative mental health outcomes like anxiety and depression, with different effects based on how social media is used. Strategies to promote digital well-being emphasize fostering healthy online behaviors and positive engagement to mitigate the negative impacts of social media on mental health. Understanding the risks and benefits of social media use is crucial in promoting positive online experiences and psychological well-being.How can textbooks promote inclusivity in the classroom on poverty?

Textbooks can promote inclusivity in the classroom by adopting innovative strategies that challenge traditional norms and cater to the needs of marginalized students. Teachers in Maharashtra have utilized digital media to connect students directly with authors and poets, ensuring a more engaging learning experience. Similarly, open textbooks initiatives at the University of Cape Town have focused on providing locally relevant content and encouraging student participation to address social injustices in education. By incorporating diverse perspectives and involving students in the creation of educational resources, textbooks can combat exclusionary practices that marginalize individuals based on gender, class, or socioeconomic status. These efforts aim to create a more inclusive learning environment that empowers all students, including those affected by poverty, to thrive academically.What are the potential interactions of retinoschisin, Aqp4 and Kir 4.1 in XLRS?

The exploration of potential interactions between retinoschisin, Aqp4 (Aquaporin-4), and Kir 4.1 (an inwardly rectifying potassium channel) in the context of X-linked juvenile retinoschisis (XLRS) is not directly addressed in the provided contexts. However, we can infer potential interactions based on the roles and interactions of retinoschisin as detailed across the studies. Retinoschisin, encoded by the RS1 gene, is a secreted protein crucial for the structural and functional integrity of the retina, interacting directly with the retinal Na/K-ATPase at the photoreceptor inner segments. This interaction is essential for anchoring retinoschisin to plasma membranes, with the glycosylated ATP1B2 subunit identified as the direct interaction partner. The deficiency of retinoschisin leads to mislocalization of the macromolecular complex and reduced protein expression of its interaction partners, although it does not affect the potassium ion currents mediated by Kv channels. Given the role of retinoschisin in regulating ERK signaling and apoptosis in retinal cells, and its involvement in MAP kinase regulation, it's plausible that retinoschisin could indirectly influence the function or expression of other membrane proteins like Aqp4 and Kir 4.1, which are critical for water and potassium homeostasis in the retina. However, the direct interactions between retinoschisin and these specific channels (Aqp4 and Kir 4.1) are not explicitly mentioned in the provided contexts. Furthermore, the therapeutic approaches for XLRS, including gene replacement therapy, do not specifically address the modulation of Aqp4 or Kir 4.1 but focus on restoring retinoschisin function. The molecular modeling of RS1 mutations and their impact on retinoschisin structure and functionalso does not directly relate to Aqp4 or Kir 4.1 but highlights the importance of retinoschisin's integrity for retinal health. In summary, while the provided contexts extensively discuss the role and interactions of retinoschisin in XLRS, they do not offer direct evidence of interactions between retinoschisin, Aqp4, and Kir 4.1. Any potential interactions would be speculative and based on the known roles of these proteins in retinal physiology.Resistance training lower blood pressure in hypertensive older adults?

Resistance training has been shown to effectively lower blood pressure in hypertensive older adults. Isometric resistance training (IRT) has been found to reduce systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP) in individuals with hypertension. Additionally, a study on elderly subjects demonstrated that a single resistance exercise with a volume of six sets of 20 repetitions maximum generated an acute post-exercise antihypertensive response that lasted for 60 minutes. Moreover, isometric resistance training has consistently shown to elicit significant reductions in blood pressure, equivalent to antihypertensive medication monotherapy, with a mean reduction of 7.4/3.3 mmHg in SBP/DBP, leading to a decrease in major cardiovascular events. Dynamic resistance training has also been effective in improving blood pressure and microvascular function in treated hypertensive men.Which are the main barriers to treatment of chronic diseases?

The main barriers to the treatment of chronic diseases include factors such as lack of medication adherence, insufficient skills of seniors, lack of user-friendly technology, and complex user interfaces. Additionally, challenges arise from inadequate access to individual data security, the non-digitization of medical data, and fragmented medical digital solutions due to varying national legislations. Furthermore, the burden of chronic diseases and multimorbidity is increasing, leading to a significant portion of primary care consultations being dedicated to chronically ill patients. The COVID-19 pandemic has exacerbated these challenges, necessitating actions to enhance the diagnosis, treatment, and follow-up of patients with chronic conditions. Efforts are required to overcome these barriers and improve the overall management of chronic diseases.