Diagnosis Of Congenital Disease Research Articles

Uplift of genetic diagnosis of rare respiratory disease using airway epithelium transcriptome analysis.

Rare genetic respiratory disease has an incidence rate of more than 1:2500 live births in Northern Europe and carries significant disease burden. Early diagnosis improves outcomes, but many individuals remain without a confident genetic diagnosis. Improved and expanded molecular testing methods are required to improve genetic diagnosis rates and thereby improve clinical outcomes. Using primary ciliary dyskinesia (PCD) as an exemplar rare genetic respiratory disease, we developed a standardized method to identify pathogenic variants using whole transcriptome RNA-sequencing (RNA-seq) of nasal epithelial cells cultured at air-liquid interface (ALI). The method was optimized using cells from healthy volunteers, and people with rhino-pulmonary disease but no diagnostic indication of PCD. We validated the method using nasal epithelial cells from PCD patients with known genetic cause. We then assessed the ability of RNA-seq to identify pathogenic variants and the disease mechanism in PCD likely patients but in whom DNA genetic testing was inconclusive. The majority of 49 targeted PCD genes were optimally identified in RNA-seq data from nasal epithelial cells grown for 21days at ALI culture. Four PCD-likely patients without a previous genetic diagnosis received a confirmed genetic diagnosis from the findings of the RNA-seq data. We demonstrate the clinical potential of RNA-seq of nasal epithelial cells to identify variants in individuals with genetically unsolved PCD. This uplifted genetic diagnosis should improve genetic counselling, enables family cascade screening, opens the door to potential personalised treatment and care approaches. This methodology could be implemented in other rare lung diseases such as cystic fibrosis.

Assessing the Utility of ColabFold and AlphaMissense in Determining Missense Variant Pathogenicity for Congenital Myasthenic Syndromes

Background/Objectives: Congenital myasthenic syndromes (CMSs) are caused by variants in >30 genes with increasing numbers of variants of unknown significance (VUS) discovered by next-generation sequencing. Establishing VUS pathogenicity requires in vitro studies that slow diagnosis and treatment initiation. The recently developed protein structure prediction software AlphaFold2/ColabFold has revolutionized structural biology; such predictions have also been leveraged in AlphaMissense, which predicts ClinVar variant pathogenicity with 90% accuracy. Few reports, however, have tested these tools on rigorously characterized clinical data. We therefore assessed ColabFold and AlphaMissense as diagnostic aids for CMSs, using variants of the CHRN genes that encode the nicotinic acetylcholine receptor (nAChR). Methods: Utilizing a dataset of 61 clinically validated CHRN variants, (1) we evaluated the possibility of a ColabFold metric (either predicted structural disruption, prediction confidence, or prediction quality) that distinguishes variant pathogenicity; (2) we assessed AlphaMissense’s ability to differentiate variant pathogenicity; and (3) we compared AlphaMissense to the existing pathogenicity prediction programs AlamutVP and EVE. Results: Analyzing the variant effects on ColabFold CHRN structure prediction, prediction confidence, and prediction quality did not yield any reliable pathogenicity indicative metric. However, AlphaMissense predicted variant pathogenicity with 63.93% accuracy in our dataset—a much greater proportion than AlamutVP (27.87%) and EVE (28.33%). Conclusions: Emerging in silico tools can revolutionize genetic disease diagnosis—however, improvement, refinement, and clinical validation are imperative prior to practical acquisition.

Investigating undiagnosed Fabry disease in young adults with ischemic stroke: A multicenter cohort study.

The global prevalence of ischemic stroke in young adults is increasing, leading to a significant social impact. Fabry disease is a recognized cause of ischemic stroke in young patients, and although disease-modifying treatments are available, further evidence is needed to confirm their effectiveness in reducing the incidence of ischemic strokes. This study aimed to identify undiagnosed Fabry disease in young adult patients with ischemic stroke in a Taiwanese cohort. This multicenter, prospective cohort study enrolled patients aged 20-55 years who had experienced an ischemic stroke or transient ischemic attack (TIA) within 10 days, from 1 January 2016 to 31 December 2020. Screening for Fabry disease was performed using a dry blood test to measure α-galactosidase activity in male patients and blood globotriaosylsphingosine (lyso-Gb3) levels in female patients. For patients with positive screen results, genetic diagnosis of Fabry disease was pursued through Sanger sequencing of the GLA gene, covering all exons and a segment of intron 4. A total of 977 patients (659 male, 68%) were enrolled from seven hospitals across Taiwan. Four patients (0.4%, all male) had positive screening results, and two patients (0.2%) were genetically diagnosed with Fabry disease. Case 1 had the GLA c.658C>T mutation and experienced ischemic stroke in the bilateral occipital regions. Case 2 had the GLA c.640-801G>A mutation and experienced an ischemic stroke in the left superficial watershed area. The prevalence of undiagnosed Fabry disease in this cohort of Taiwanese young adults with ischemic stroke or TIA was 0.3% among the young male population. Understanding the prevalence of undiagnosed Fabry disease in young adults with ischemic stroke could help shape future Fabry disease screening policies. The collected data will be available upon reasonable request from the corresponding author.

The debate on artificial insemination in medical-moral reflection in Italy over the last decade

Talking today about artificial insemination certainly no longer arouses wonder. Man's lordship over creation, in fact, registers a singular breadth with unprecedented and surprising results, especially in the field of the physio-pathology of reproduction: intrauterine diagnosis of genetic diseases, control or even sex determination, the most diverse genetic experiments for therapeutic or research purposes; attempts at extracorporeal fertilisation.

Political-organisational aspects for the prevention of genetic diseases

The explosive advances in medical genetics are, as is well known, very recent, but they already constitute major references in the preparation of the new models of health action postulated by the establishment of the national health service. They have made possible and at the same time necessitated extensive legislative and organisational design work for the prevention, diagnosis and treatment of genetic diseases. Translated with DeepL.com (free version)

The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China.

Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnosis in patients suspected of genetic disorders. This retrospective analysis included 144 patients diagnosed by singleton-WES Trio-WES between January 2021 and December 2023. We investigated the relevance of diagnosis rates with age, clinical presentation, and sample type. Among the 144 patients, 61 were diagnosed, yielding an overall diagnostic rate of 42.36%, with Trio-WES demonstrating a significantly higher diagnostic rate of 51.43% (36/70) compared to singleton-WES at 33.78% (25/74) (p < 0.05). Global developmental delay had a diagnosis rate of 67.39%, significantly higher than muscular hypotonia at 30.43% (p < 0.01) among different clinical phenotypic groups. Autosomal dominant disorders accounted for 70.49% (43/61) of positive cases, with autosomal abnormalities being fivefold more prevalent than sex chromosome abnormalities. Notably, sex chromosome abnormalities were more prevalent in males (80%, 8/10). Furthermore, 80.56% (29/36) of pathogenic variants were identified as de novo mutations through Trio-WES. These findings highlight the effectiveness of WES in identifying genetic variants, and elucidating the molecular basis of genetic diseases, ultimately enabling early diagnosis in affected children.

Prenatal diagnosis of genetic diseases

For the last fifteen years or so, the application of new techniques has entered medical practice, and has become widespread, that make it possible to establish the existence of particular conditions in the foetus, capable of causing alterations in its development or giving rise to serious pathologies later or later after birth. Techniques therefore offering the possibility of making prenatal genetic ‘diagnoses’ and ‘prognoses’.

Diagnosis and Screening of Velocardiofacial Syndrome by Evaluating Facial Photographs Using a Deep Learning-Based Algorithm.

Early detection of rare genetic diseases, including velocardiofacial syndrome (VCFS), is essential for patient well-being. However, their rarity and limited clinical experience of physicians make diagnosis challenging. Deep learning algorithms have emerged as promising tools for efficient and accurate diagnosis. This study investigates the use of a deep learning algorithm to develop a face recognition model for diagnosing VCFS. The study employed publicly available labeled face datasets to train the multitask cascaded convolutional neural networks (MTCNN) model. Subsequently, we examined the binary classification performance for diagnosing VCFS using the most efficient face recognition model. A total of 98 VCFS patients (920 facial photographs) and 91 non-VCFS controls (463 facial photographs) were randomly divided into training and test sets. Additionally, we analyzed whether the classification results matched the known facial phenotype of VCFS. The face recognition model demonstrated high accuracy, ranging from 94% to 99%, depending on the training dataset. The accuracy of the binary classification diagnostic model varied from 81% to 88% when evaluating with photographs taken at various angles, but reached 95% evaluating with frontal photographs only. Gradient-weighted class activation mapping heatmap revealed the high importance level of perinasal and periorbital areas, exhibiting consistency with the conventional facial phenotypes of VCFS. This study shows the feasibility and effectiveness of MTCNN-based model for detecting VCFS solely from facial photographs. The high accuracy underscores the potential of deep learning in aiding early diagnosis of rare genetic diseases, facilitating timely interventions for patient care.

Exome wide association study for blood lipids in 1,158,017 individuals from diverse populations.

Rare coding alleles play crucial roles in the molecular diagnosis of genetic diseases. However, the systemic identification of these alleles has been challenging due to their scarcity in the general population. Here, we discovered and characterized rare coding alleles contributing to genetic dyslipidemia, a principal risk for coronary artery disease, among over a million individuals combining three large contemporary genetic datasets (the Million Veteran Program, n = 634,535, UK Biobank, n = 431,178, and the All of Us Research Program, n = 92,304) totaling 1,158,017 multi-ancestral individuals. Unlike previous rare variant studies in lipids, this study included 238,243 individuals (20.6%) from non-European-like populations. Testing 2,997,401 rare coding variants from diverse backgrounds, we identified 800 exome-wide significant associations across 209 genes including 176 predicted loss of function and 624 missense variants. Among these exome-wide associations, 130 associations were driven by non-European-like populations. Associated alleles are highly enriched in functional variant classes, showed significant additive and recessive associations, exhibited similar effects across populations, and resolved pathogenicity for variants enriched in African or South-Asian populations. Furthermore, we identified 5 lipid-related genes associated with coronary artery disease (RORC, CFAP65, GTF2E2, PLCB3, and ZNF117). Among them, RORC is a potentially novel therapeutic target through the down regulation of LDLC by its silencing. This study provides resources and insights for understanding causal mechanisms, quantifying the expressivity of rare coding alleles, and identifying novel drug targets across diverse populations.

Endocrinopathy due to proproteinkovertase 1/3 deficiency: primary enteropathy, diabetes insipidus, secondary hypothyroidism

Proprotein convertase 1/3 (PC1/3) deficiency is an autosomal recessive disease caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK 1)gene, associated with severe malabsorptive diarrhea, obesity and some endocrine abnormalities. Proprotein convertase 1/3 is acalcium-dependent serine endoprotease involved in the proteolytic processing of various prohormones (peptide hormones in enteroendocrine cells that are necessary for the absorption of nutrients and is also expressed in the arcuate and paraventricular nuclei of the hypothalamus, in the beta cells of the pancreas) in their bioactive forms. The onset of the disease in the neonatal period of life is characterized by aclinical picture of severe malabsorption diarrhea, accompanied by developmental delays, and requires long-term parenteral nutrition. As the disease progresses, additional endocrine abnormalities develop, including diabetes insipidus, growth hormone deficiency, primary hypogonadism, adrenal insufficiency, hypothyroidism, and obesity. We conducted aprospective observation of apatient with agenetic disease due to proprotein convertase 1/3 deficiency confirmed during follow-up. The patient was examined and treated at the State Novosibirsk Regional Clinical Hospital in Novosibirsk for 11 months, with repeated (3-fold) hospitalizations. Purpose: to demonstrate the features of the onset and course of the disease, as well as the difficulties in verifying the clinical diagnosis of an ultra-rare genetic disease from the category of endocrinopathies, the complexity of medical support and therapy. Apeculiarity of this case is the fact that the identified mutation in the gene was not previously registered in control Russian samples of the genetic mutation of proprotein convertase 1/3 deficiency, as well as apreviously undescribed variant of the nucleotide sequence in exon 4 of the PCSK1 gene in aheterozygous state and was not registered in control samples gnomAD and RUSeq. Proprotein convertase 1/3 deficiency is adisease that is amultidisciplinary problem, since etiopathogenetic therapy has not yet been developed. The disease has achronic course with constant relapses of intestinal syndrome, is difficult to manage with symptomatic treatments and, as it progresses, has ahigh risk of developing additional endocrinopathies and death. All of the above emphasizes the need for early diagnosis and selection of rational replacement and accompanying therapy to save the lives of patients.

Assessing the utility of large language models for phenotype-driven gene prioritization in the diagnosis of rare genetic disease

Phenotype-driven gene prioritization is fundamental to diagnosing rare genetic disorders. While traditional approaches rely on curated knowledge graphs with phenotype-gene relations, recent advancements in large language models (LLMs) promise a streamlined text-to-gene solution. In this study, we evaluated five LLMs, including two generative pre-trained transformers (GPT) series and three Llama2 series, assessing their performance across task completeness, gene prediction accuracy, and adherence to required output structures. We conducted experiments, exploring various combinations of models, prompts, phenotypic input types, and task difficulty levels. Our findings revealed that the best-performed LLM, GPT-4, achieved an average accuracy of 17.0% in identifying diagnosed genes within the top 50 predictions, which still falls behind traditional tools. However, accuracy increased with the model size. Consistent results were observed over time, as shown in the dataset curated after 2023. Advanced techniques such as retrieval-augmented generation (RAG) and few-shot learning did not improve the accuracy. Sophisticated prompts were more likely to enhance task completeness, especially in smaller models. Conversely, complicated prompts tended to decrease output structure compliance rate. LLMs also achieved better-than-random prediction accuracy with free-text input, though performance was slightly lower than with standardized concept input. Bias analysis showed that highly cited genes, such as BRCA1, TP53, and PTEN, are more likely to be predicted. Our study provides valuable insights into integrating LLMs with genomic analysis, contributing to the ongoing discussion on their utilization in clinical workflows.

Noninvasive Prenatal Genetic Screening of Cell-Free Fetal DNA for Early Prediction of β-Thalassemia Using Fiber Optic Nanogold-Linked Sorbent Assay.

β-Thalassemia is a prevalent type of severe inherited chronic anemia, primarily identified in developing countries. The identification of single nucleotide polymorphisms (SNPs) plays a vital role in the early diagnosis of genetic diseases. Here, we reported the development of an amplification-free fiber optic nanogold-linked sorbent assay method using a fiber optic particle plasmon resonance (FOPPR) biosensor for rapid and ultrasensitive detection of SNPs. Herein, MutS protein was selected as the biorecognition capture probe and immobilized on the sensing region to capture the target mutant DNA, which was hybridized with a single-base mismatched single-stranded DNA labeled by a gold nanoparticle (AuNP). The AuNP acts as a signaling agent to be detected by the FOPPR biosensor when it is bound on the fiber core surface. The method effectively differentiates mismatched double-stranded DNA by MutS protein from perfectly matched/complementary dsDNA. It exhibits an impressively low detection limit for the detection of SNPs at approximately 10-16 M using low-cost sensor chips and devices. By determination of the ratio of mutant DNA to normal DNA in cell-free genomic DNA from blood samples, this method is promising for diagnosing β-thalassemia in fetuses without invasive testing techniques.

Emphasis on the importance of comprehensive clinical and genetic analysis - spinal muscular atrophy combined with phenylketonuria: A case report.

Both spinal muscular atrophy (SMA) and Phenylketonuria (PKU) are caused by biallelic pathogenic mutations. However, there has been no report on case who suffering from both diseases simultaneously. SMA mainly affects the motor function while PKU may have an impact on both the intelligence and motor function. But if only 1 disease is treated while neglecting the other, the treatment effect will be compromised. Here, for the first time, we report a case from China diagnosed with both these diseases and treated properly. A boy was admitted to the Children's Hospital Affiliated to Shandong University (Jinan, China) due to "limb weakness for 19 months" when he was 22 months old. Considering that the child's motor function development is delayed, we made a comprehensive examinations including inherited metabolic diseases and found a significantly increase of phenylalanine concentration in the blood which indicating PKU. Combined with his typical clinical manifestations of SMA, target capture sequencing followed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) technologies were used for genetic confirmation. SMA and PKU was confirmed. The child was treated with risdiplam and low phenylalanine formula immediately when he was diagnosed with both SMA and PKU. The child showed remarkable improvement in motor function and significant decrease of blood phenylalanine concentration after treatment. To our knowledge, this is the first reported case of SMA combined with PKU. This case expands our understanding of diagnosis for synchronous SMA and PKU and highlights the importance of comprehensive examinations and the utilizing of various genetic testing methods to make an accurate diagnosis of genetic diseases, which may help avoiding the progressive damage caused by certain genetic disease with insidious clinical symptoms.

Navigating the CRISPR/Cas Landscape for Enhanced Diagnosis and Treatment of Wilson's Disease.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system continues to evolve, thereby enabling more precise detection and repair of mutagenesis. The development of CRISPR/Cas-based diagnosis holds promise for high-throughput, cost-effective, and portable nucleic acid screening and genetic disease diagnosis. In addition, advancements in transportation strategies such as adeno-associated virus (AAV), lentiviral vectors, nanoparticles, and virus-like vectors (VLPs) offer synergistic insights for gene therapeutics in vivo. Wilson's disease (WD), a copper metabolism disorder, is primarily caused by mutations in the ATPase copper transporting beta (ATP7B) gene. The condition is associated with the accumulation of copper in the body, leading to irreversible damage to various organs, including the liver, nervous system, kidneys, and eyes. However, the heterogeneous nature and individualized presentation of physical and neurological symptoms in WD patients pose significant challenges to accurate diagnosis. Furthermore, patients must consume copper-chelating medication throughout their lifetime. Herein, we provide a detailed description of WD and review the application of novel CRISPR-based strategies for its diagnosis and treatment, along with the challenges that need to be overcome.

Advancements in Research on Genetic Kidney Diseases Using Human-Induced Pluripotent Stem Cell-Derived Kidney Organoids.

Genetic or hereditary kidney disease stands as a pivotal cause of chronic kidney disease (CKD). The proliferation and widespread utilization of DNA testing in clinical settings have notably eased the diagnosis of genetic kidney diseases, which were once elusive but are now increasingly identified in cases previously deemed CKD of unknown etiology. However, despite these diagnostic strides, research into disease pathogenesis and novel drug development faces significant hurdles, chiefly due to the dearth of appropriate animal models and the challenges posed by limited patient cohorts in clinical studies. Conversely, the advent and utilization of human-induced pluripotent stem cells (hiPSCs) offer a promising avenue for genetic kidney disease research. Particularly, the development of hiPSC-derived kidney organoid systems presents a novel platform for investigating various forms of genetic kidney diseases. Moreover, the integration of the CRISPR/Cas9 technique into this system holds immense potential for efficient research on genetic kidney diseases. This review aims to explore the applications of in vitro kidney organoids generated from hiPSCs in the study of diverse genetic kidney diseases. Additionally, it will delve into the limitations of this research platform and outline future perspectives for advancing research in this crucial area.

Exploring the clinical utility of exome sequencing/Mono, Duo, Trio in prenatal testing: a retrospective study in a tertiary care centre in South India.

With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants. This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020-2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing. The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant. Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.

Facing the challenges to shorten the diagnostic odyssey: first Whole Genome Sequencing experience of a Colombian cohort with suspected rare diseases

Exome and genome sequencing (ES/GS) are routinely used for the diagnosis of genetic diseases in developed countries. However, their implementation is limited in countries from Latin America. We aimed to describe the results of GS in patients with suspected rare genetic diseases in Colombia. We studied 501 patients from 22 healthcare sites from January to December 2022. GS was performed in the index cases using dried blood spots on filtercards. Ancestry analysis was performed under iAdmix. Multiomic testing was performed when needed (biomarker, enzymatic activity, RNA-seq). All tests were performed at an accredited genetic laboratory. Ethnicity prediction data confirmed that 401 patients (80%) were mainly of Amerindian origin. A genetic diagnosis was established for 142 patients with a 28.3% diagnostic yield. The highest diagnostic yield was achieved for pathologies with a metabolic component and syndromic disorders (p < 0.001). Young children had a median of 1 year of diagnostic odyssey, while the median time for adults was significantly longer (15 years). Patients with genetic syndromes have spent more than 75% of their life without a diagnosis, while for patients with neurologic and neuromuscular diseases, the time of the diagnostic odyssey tended to decrease with age. Previous testing, specifically karyotyping or chromosomal microarray were significantly associated with a longer time to reach a definitive diagnosis (p < 0.01). Furthermore, one out of five patients that had an ES before could be diagnosed by GS. The Colombian genome project is the first Latin American study reporting the experience of systematic use of diagnostic GS in rare diseases.

Specification for genetic diagnosis of congenital heart disease

Congenital heart disease (CHD) is one of the most common congenital malformations and a major cause of mortality among neonates and children. Conventional methods for the diagnosis of CHD have relied on clinical features and imaging findings. With the rapid development of genetic techniques, to identify the cause of CHD through genetic diagnosis has gained great significance for the early diagnosis, treatment, and prevention of CHD. However, currently there is still a lack of norms and standards for the genetic diagnosis of CHD. In view of this, experts from the relevant fields have formulated the present norm by integrating the latest research advances on CHD-related genes with the current clinical practice on the diagnosis and treatment of CHD and status quo of genetic diagnosis in China. The norm has been recommended by the Cardiology Section of the Chinese Medical Education Association, the Medical Genetics Branch and the Heart Group of Pediatric Surgery Branch of the Chinese Medical Association, which has formulated the procedures and norms of genetic testing, prenatal diagnosis, and genetic counseling for CHD, with an aim to provide reference for clinicians as the standards for the integrated diagnosis, early treatment, and prevention of CHD.

Expert consensus on the test development and preliminary implementation of whole genome sequencing for fetal structural abnormalities

Fetal structural anomalies and birth defects are primarily caused by genetic variants such as chromosomal number abnormalities, copy number variations (CNV), single nucleotide variants (SNV), and small insertions and deletions (indel). Whole-genome sequencing (WGS) based on next-generation sequencing (NGS) as an emerging technology for genetic disease diagnosis can detect the aforementioned types of variants. In recent years, high-depth WGS (> 30×) for prenatal diagnosis has also become available, and proved to be practical for unraveling the genetic etiology of fetal developmental abnormalities. To facilitate clinical practice, test development and preliminary implementation of WGS for diagnosing fetal structural anomalies, we have formulated a consensus over the application of WGS in prenatal diagnosis by compiling previously published consensuses, guidelines, and research findings to provide a guidance on data analysis, reporting recommendations, and consultation of prenatal WGS results.

Knowledge of genetics and attitudes toward genetic testing among university students in Indonesia.

The development in human genetics must be tracked with the knowledge to provide support and positive attitudes towards genetic research and its healthcare applications, including genetic testing. Unfortunately, there has been a delay in enacting public policies related to the genetics professionals as well as the diagnosis, treatment, and prevention of genetic diseases in Indonesia. This research was conducted to build an overview of genetic knowledge and public attitudes toward genetic testing among Indonesian undergraduates. This cross-sectional study involved undergraduate students selected using the convenience sampling method. The questionnaire consisted of two parts: a true/false questionnaire (16 statements) regarding knowledge of genetics and a 5-points Likert scale questionnaire (27 statements) pertaining to attitudes towards genetic testing. A total of 1596 undergraduate students completed online questionnaire. The highest knowledge score and the most positive overall attitudes were observed in the healthcare-related majors compared to those who studied science and technology and social and humanity. A weak positive correlation was observed between knowledge and attitude toward genetic testing (Pearson's r = 0.206, p < 0.001). Undergraduate students from healthcare-related majors displayed better in both knowledge of genetics and had more positive attitudes toward genetic testing.