The potential and translational application of infant genetic research.

In the current genomic revolution, the infancy life stage is the most neglected. Although clinical genetics recognizes the value of early identification in infancy of rare genetic causes of disorders and delay, common genetic variation is almost completely ignored in research on infant behavioral and neurodevelopmental traits. In this Perspective, we argue for a much-needed surge in research on common genetic variation influencing infant neurodevelopment and behavior, findings that would be relevant for all children. We now see convincing evidence from different research designs to suggest that developmental milestones, skills and behaviors of infants are heritable and thus are suitable candidates for gene-discovery research. We highlight the resources available to the field, including genotyped infant cohorts, and we outline, with recommendations, special considerations needed for infant data. Therefore, infant genetic research has the potential to impact basic science and to affect educational policy, public health and clinical practice.

Perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research.

BACKGROUND: Genetic research can yield information that is unrelated to the study's objectives but may be of clinical or personal interest to study participants. There is an emerging but controversial responsibility to return some genetic research results, however there is little evidence available about the views of genomic researchers and others on the African continent. METHODS: We conducted a continental survey to solicit perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research. RESULTS: A total of 110 persons participated in the survey with 51 complete and 59 incomplete surveys received. Data was summarised using descriptive analysis. Overall, our respondents believed that individual genetic research results that are clinically actionable should be returned to study participants apparently because participants have a right to know things about their health, and it might also be a means for research participation to be recognized. Nonetheless, there is a need for development of precise guidance on how to return individual genetic research findings in African genomics research. DISCUSSION: Participants should receive information that could promote a healthier lifestyle; only clinically actionable findings should be returned, and participants should receive all important information that is directly relevant to their health. Nevertheless, detailed guidelines should inform what ought to be returned. H3Africa guidelines stipulate that it is generally considered good practice for researchers to feedback general study results, but there is no consensus about whether individual genomic study results should also be fed back. The decision on what individual results to feedback, if any, is very challenging and the specific context is important to make an appropriate determination.

Genetic research within Indigenous communities: Engagement opportunities and pathways forward.

PURPOSE: Against a historical backdrop of researchers who violated trust through lack of benefit sharing, transparency, and engagement, efforts are underway to develop better approaches for genetic and genomic research with Indigenous communities. To increase engagement, there is a need to understand factors that affect researcher and community collaborations. This study aimed to understand the barriers, challenges, and facilitators of Indigenous Peoples in the United States participating in genetic research. METHODS: We conducted 42 semistructured interviews with Tribal leaders, clinicians, researchers, policy makers, and Tribal research review board members across the United States to explore perceived risks, benefits, barriers, and facilitators of genetic research participation. RESULTS: Participants, identifying as Indigenous (88%) or non-Indigenous allies (12%), described their concerns, hesitancy, and fears about genetic research, as well as the roles of trust, transparency, and respect for culture in facilitating partnerships. Previous harms-such as sample and data misuse, stigmatization, or misrepresentation by researchers-revealed strategies for building trust to create more equitable and reciprocal research partnerships. CONCLUSION: Participants in this study offered strategies for increasing genetic research engagement. The pathway forward should foster transparent research policies and practices to facilitate informed research that supports the needs and priorities of participants, communities, and researchers.

Addressing Barriers and Facilitators to African Americans' and Hispanics' Participation in Clinical and Genomic Research Through a Bioethical Sensitive Video.

Research advances on effective methods to prevent, diagnose, and treat cancer continue to emerge through clinical and genomic research. Most clinical trial and genomic research participants identify as White which limits the generalizability of research findings to non-White populations. With the development and access to technology, digital delivery of salient and tailored health education may provide innovative pathways to increase representation of African Americans (AA) and Hispanics in research. This project focused on the creation of a bioethical sensitive education video aimed at increasing participation in clinical trials and genomic research by bringing together experts from the community, healthcare, biomedical research, and public health. The goal was to utilize existing educational resources to create a tailored message to address AA/Hispanics' beliefs, values, and bioethical concerns related to participation in clinical and genomic research. Models of behavior change and communication theories were leveraged to frame key components of the message, which then informed the framework for the animated video. Development of the video consisted of six iterative phases: 1) writing sessions; 2) storyboarding; 3) animating; 4) screening/revisions; 5) acceptability testing; 6) finalization. The final animated video is approximately 5 min in length and covers several topics including the goal of clinical research, disparities in research participation, bioethical concerns, and genomic research regulations. Increasing AA and Hispanic participation in clinical and genomic research is imperative to achieving health equity. Tailored messages via short videos may assist in addressing the barriers and facilitators towards research participation and increase intentions to enroll in trials.

Understanding the Gap: A Cross-Sectional Survey of ELSI Scholars' Dissemination Practices and Translation Goals.

BACKGROUND: Researchers engaged in the study of the ethical, legal, and social implications (ELSI) of genetics and genomics are often publicly funded and intend their work to be in the public interest. These features of U.S. ELSI research create an imperative for these scholars to demonstrate the public utility of their work and the expectation that they engage in research that has potential to inform policy or practice outcomes. In support of the fulfillment of this "translational mandate," the Center for ELSI Resources and Analysis (CERA), funded by the National Human Genome Research Institute (NHGRI), aims to facilitate community-informed, ELSI research results synthesis and dissemination. However, little is known about how ELSI research scholars define the goals of translation and imagine the intended users of their research findings. METHODOLOGY: We distributed a Qualtrics survey to ELSI scholars that aimed to determine: (1) researchers' expectations for their research findings in relation to policy or practice outcomes, (2) the stakeholder groups researchers believe could benefit from their research findings, and (3) the methods researchers use to foster the uptake of their findings by those stakeholders. RESULTS: Most ELSI researchers surveyed thought there were stakeholders that could benefit from their research findings, including health care professionals, at-risk individuals, patients, and their family members, policy-makers, and researchers/scientists, and expected their research findings to inform the creation or revision of laws, policies, or practice guidelines. Most researchers planned to disseminate findings directly to relevant stakeholders, with fewer expecting dissemination support from research funders, universities, or other entities. CONCLUSION: The broad range of research topics, disciplines, and set of potential end users represented in ELSI reseach complicate the work of a knowledge broker. Nonetheless, the CERA can play an important role in disseminating ELSI results to relevant stakeholders. Further research should explore outreach mechanisms.

ONT read assembly of the black rhino genome.

OBJECTIVES: The black rhinoceros (Diceros bicornis) is an endangered mammal for which a captive breeding program is part of the conservation effort. Black rhinos in zoo's often suffer from chronic infections and heamochromatosis. Furthermore, breeding is hampered by low male fertility. To aid a research project studying these topics, we sequenced and assembled the genome of a captive male black rhino using ONT sequencing data only. DATA DESCRIPTION: This work produced over 100 Gb whole genome sequencing reads from whole blood. These were assembled into a 2.47 Gb draft genome consisting of 834 contigs with an N50 of 29.53 Mb. The genome annotation was lifted over from an available genome annotation for black rhino, which resulted in the retrieval of over 99% of gene features. This new genome assembly will be a valuable resource in for conservation genetic research in this species.

[Studies on the association of genes with language disorders in the post-genomic era].

Since genetic research entered the post-genomic era, the high heritability of language disorders has been confirmed. A variety of genetic-related diseases may cause various types of language disorders in children and/or adults. This article has summarized language disorders and their underlying mechanisms by searching the Web of Science database over the last decade, and combed the genetic researches for dyslexia, frontotemporal degeneration, specific language disorder, childhood speech apraxia and other single diseases that are strongly associated with the language disorders. It also provided a discussion over the co-occurrence of multiple diseases, with an aim to revealing the genetic association and/or pathogenetic mechanism in order to provide inspiration for the prevention, diagnosis, and treatment of language disorders.

What do parents of nonverbal and minimally verbal autistic children think about genomic autism research?

LAY ABSTRACT: In Summer 2021, a genomic study of autism, Spectrum 10 K, was paused due to backlash from the autistic and autism communities. This raised important questions about how these communities perceive genomic research. The Personal Experiences of Autism and Perceptions of DNA-based research study was established to address this issue among a range of sub-groups within these communities. Twenty parents of nonverbal or minimally verbal autistic children took part in the current study. Data were provided in diverse formats including online interviews, telephone interviews, and writing. This approach was co-produced with autistic experts by experience and involved a parent of a minimally verbal autistic child. Data were analysed using reflexive Thematic Analysis. We found that participants were supportive of autism research, including some genomic research, as long as it is designed to support autistic people and is ethical and transparent. However, while some believed that polygenic scores, genomic predictors of the statistical probability of being autistic, would be helpful, others argued that this would only be true in an ideal world and that the world is too far from ideal. Participants felt excluded from the autistic and autism communities and that the dominant voices in those communities do not represent them or their children. We concluded that genomic researchers need to work with the autistic and autism communities to design future work, and that it is important to ensure a representative range of voices are heard.

Artificial replication cohort: Leveraging AI-fabricated data for genetic studies.

Recent advancements in artificial intelligence (AI) present both opportunities and challenges within the scientific community. This study explores the capability of AI to replicate findings from genetic research, focusing on findings from prior work. Using an AI model without exposing any raw data, we created a dataset that closely mirrors the results of our original study, illustrating the ease of fabricating datasets with authenticity. This approach highlights the risks associated with AI misuse in scientific research. The study emphasizes the critical importance of maintaining the integrity of scientific inquiry in an era increasingly influenced by advanced AI technologies.

Compound heterozygosity for Southeast Asian hereditary persistence of fetal hemoglobin and ß0-thalassemia results in thalassemia intermedia: Pedigree analysis and genetic research in a family from South China. A case report.

RATIONALE: Compound heterozygotes for deletional ß-thalassemia can be difficult to diagnose due to its diverse clinical presentations and no routine screenings. This can lead to disease progression and delay in treatment. PATIENT CONCERNS: We reported pedigree analysis and genetic research in a family with rare ß-thalassemia. DIAGNOSIS: Pedigree analysis and genetic research demonstrated that the patient was a compound heterozygote for ß-thalassemia CD17/Southeast Asian hereditary persistence of fetal hemoglobin deletion, inherited from the parents. Magnetic resonance imaging T2* examination revealed severe iron deposition in the liver. Echocardiography revealed endocardial cushion defect. INTERVENTIONS: The patient was treated with Deferasirox after receiving the final molecular genetic diagnosis. The initial once-daily dose of Deferasirox was 20 mg/kg/d. OUTCOMES: The patient discontinued the medication three months after the first visit. Two years later, the patient visited the Department of Hepatobiliary and Pancreatic Diseases. He was recommended to undergo splenectomy after surgical repair of the congenital heart disease. However, the patient refused surgical treatment because of the economic burden. LESSONS: We report that fetal hemoglobin is a sensitive indicator for screening large deletions of the ß-globin gene, which can be effectively confirmed by the multiplex ligation-dependent probe amplification assay. In non-transfusion-dependent thalassemia patients, iron status assessment should be regularly performed, and iron chelation treatment should be initiated early. This case will provide insights for the diagnosis of rare genotypes of ß-thalassemia and has important implications for genetic counseling.

ASAP: a platform for gene functional analysis in Angelica sinensis.

BACKGROUND: Angelica sinensis (Danggui), a renowned medicinal orchid, has gained significant recognition for its therapeutic effects in treating a wide range of ailments. Genome information serves as a valuable resource, enabling researchers to gain a deeper understanding of gene function. In recent times, the availability of chromosome-level genomes for A. sinensis has opened up vast opportunities for exploring gene functionality. Integrating multiomics data can allow researchers to unravel the intricate mechanisms underlying gene function in A. sinensis and further enhance our knowledge of its medicinal properties. RESULTS: In this study, we utilized genomic and transcriptomic data to construct a coexpression network for A. sinensis. To annotate genes, we aligned them with sequences from various databases, such as the NR, TAIR, trEMBL, UniProt, and SwissProt databases. For GO and KEGG annotations, we employed InterProScan and GhostKOALA software. Additionally, gene families were predicted using iTAK, HMMER, OrholoFinder, and KEGG annotation. To facilitate gene functional analysis in A. sinensis, we developed a comprehensive platform that integrates genomic and transcriptomic data with processed functional annotations. The platform includes several tools, such as BLAST, GSEA, Heatmap, JBrowse, and Sequence Extraction. This integrated resource and approach will enable researchers to explore the functional aspects of genes in A. sinensis more effectively. CONCLUSION: We developed a platform, named ASAP, to facilitate gene functional analysis in A. sinensis. ASAP ( www.gzybioinformatics.cn/ASAP ) offers a comprehensive collection of genome data, transcriptome resources, and analysis tools. This platform serves as a valuable resource for researchers conducting gene functional research in their projects, providing them with the necessary data and tools to enhance their studies.

Community engagement in genetics and genomics research: a qualitative study of the perspectives of genetics and genomics researchers in Uganda.

BACKGROUND: Generally, there is unanimity about the value of community engagement in health-related research. There is also a growing tendency to view genetics and genomics research (GGR) as a special category of research, the conduct of which including community engagement (CE) as needing additional caution. One of the motivations of this study was to establish how differently if at all, we should think about CE in GGR. AIM: To assess the perspectives of genetics and genomics researchers in Uganda on CE in GGR. METHOD: A cross-sectional qualitative study was conducted at Makerere University and Uganda Virus Research Institute. Twenty-five individuals participated, the majority being male (sixteen). Participants included nineteen genetics and genomics researchers (researchers and research coordinators), two CE officers, three nurses and one nursing counsellor. Data were collected using in-depth interviews and analyzed in a thematic manner using NVivo version 12 Plus. STUDY FINDINGS: Thirteen of the respondents had conducted CE in their GGR in either a geographical and disease-specific community. Some respondents said CE principles are the same and there is no need for special consideration for CE in GGR. Others gave ethical issues in GGR that require special consideration for CE in such research and these were categorized into six themes: GGR is new to communities, Difficulty in communicating GGR by the researchers, Genes are shared in communities, Cultural sensitivities against GGR, Community attitude toward GGR, Some GGR studies take long to end, and Negotiation of research benefits. Special considerations for CE when conducting GGR were suggested and categorized into seven themes: creating awareness of GGR in communities, obtaining both community acceptance and individual consent, CE team composition, involve communities in solving GGR challenges, prolong CE in some GGR, develop guidelines for CE in GGR, and legal considerations on GGR. CONCLUSION: GGR was characterized by special issues that require special CE considerations for such research.

More than a decade of genetic research on the Denisovans.

Denisovans, a group of now extinct humans who lived in Eastern Eurasia in the Middle and Late Pleistocene, were first identified from DNA sequences just over a decade ago. Only ten fragmentary remains from two sites have been attributed to Denisovans based entirely on molecular information. Nevertheless, there has been great interest in using genetic data to understand Denisovans and their place in human history. From the reconstruction of a single high-quality genome, it has been possible to infer their population history, including events of admixture with other human groups. Additionally, the identification of Denisovan DNA in the genomes of present-day individuals has provided insights into the timing and routes of dispersal of ancient modern humans into Asia and Oceania, as well as the contributions of archaic DNA to the physiology of present-day people. In this Review, we synthesize more than a decade of research on Denisovans, reconcile controversies and summarize insights into their population history and phenotype. We also highlight how our growing knowledge about Denisovans has provided insights into our own evolutionary history.

Bruno Schulz's 1936 book "Methodology of medical genetic research particularly with regard to psychiatry".

In 1936, Bruno Schulz published the first detailed, book-length review of the methodology of psychiatric genetic research, based on his experiences at the German Research Institute of Psychiatry. Emphasis is placed on proper selection of relatives and the ascertainment corrections required for Mendelian transmission models. Twin studies are considered as is the impact of reduced fertility on patterns of risk. For the field work, Schulz emphasizes the importance of trust-building, confidentiality, collateral informants, and the use of medical and other administrative records, all ideally stored in personal files. Several methods of age-correction are reviewed. Schulz provides detailed algebraic treatments of these and other problems, including tests for etiologic homogeneity, with worked examples. He emphasizes two fundamental concerns in psychiatric genetics research: (i) its inter-dependency with the optimal diagnostic boundaries, which are rarely known and (ii) the genetic homogeneity of clinical samples. Given these problems, he is pessimistic about finding Mendelian transmission patterns. He assesses the predominant 19th-century method of psychiatric genetic investigation-"hereditary burden"-to be crude and biased by family size. Although written at a time of consolidation of Nazi power in Germany, this book nowhere endorses their racial/eugenic policies and can be seen as subtly questioning them.

Genetics of 21-hydroxylase deficiency: Clinical presentation should guide the investigation.

A young couple applied for preconception counseling because of a case of congenital adrenal hyperplasia in the family. They were concerned about their risk of giving birth to a child with classic congenital adrenal hyperplasia. The case presented here demonstrates the complexity of the genetics of 21-hydroxylase deficiency and the way the clinical presentation should guide the genetic inquiry.

A group B Streptococcus indexed transposon mutant library to accelerate genetic research on an important perinatal pathogen.

IMPORTANCE: Group B Streptococcus (GBS) is a significant global cause of serious infections, most of which affect pregnant women, newborns, and infants. Studying GBS genetic mutant strains is a valuable approach for learning more about how these infections are caused and is a key step toward developing more effective preventative and treatment strategies. In this resource report, we describe a newly created library of defined GBS genetic mutants, containing over 1,900 genetic variants, each with a unique disruption to its chromosome. An indexed library of this scale is unprecedented in the GBS field; it includes strains with mutations in hundreds of genes whose potential functions in human disease remain unknown. We have made this resource freely available to the broader research community through deposition in a publicly funded bacterial maintenance and distribution repository.