Genetic Association Studies - Science method

The integration of genetic engineering, biotechnology, and bioinformatics has transformed modern crop improvement strategies, enabling the development of plant varieties with enhanced yield stability and quality, increasing nutritional value, reducing environmental impact and stronger resistance to pests and environmental stresses. Genetic engineer...

Pathogenic variants in γ‐aminobutyric acid type A (GABAA) receptor subunit genes are increasingly associated with epilepsy and neurodevelopmental disorders. Pathogenic variants in GABRA2, encoding the α‐2 subunit of GABAA receptors, have been recently reported. This study aims to better delineate the phenotypic spectrum of GABRA2 pathogenic variant...

Chili peppers (Capsicum spp.), a globally significant crop revered for their nutritional, economic, and cultural importance, are increasingly imperiled by the converging burdens of climate-induced abiotic stresses, including drought, heat, and salinity, and relentless biotic assaults from pathogens and insect herbivores. These overlapping stressors...

Incontinentia pigmenti (IP) is a rare X-linked dominant condition that leads to variable abnormalities affecting the skin, hair, nails, teeth, eyes, and central nervous system. It is associated with variants in the IKBKG (also known as NEMO ) gene, and recent findings have identified gene conversion involving the IKBKG pseudogene ( IKBKGP1 ) as a c...

A major challenge lies in discovering, emphasizing, and characterizing human gene-disease and gene-gene associations. The limitations of data on the role of human gene products in substance use disorder (SUD) makes it challenging to transition from genetic associations to actionable insights. The integration of data from multiple diverse sources, i...

Background Brachydactyly type E (BDE) is characterized by variable shortening of metacarpals or metatarsals, often involving phalanges. It may occur as an isolated anomaly or as part of congenital syndromes. With advancements in molecular diagnostic technologies, how genetic testing enhances the precise diagnosis of BDE remains unclear. Our aims we...

Identifying causative genes from patient phenotypes remains a significant challenge in precision medicine, with important implications for the diagnosis and treatment of genetic disorders. We propose a novel graph-based approach for predicting causative genes from patient phenotypes, with or without an available list of candidate genes, by integrat...

This is a cross‐sectional study on the clinical and genetic data of a cohort of 49 Stargardt disease patients visiting a tertiary eye hospital in India. Analysis of the clinical parameters showed an association of lower BCVA with the presence of flecks outside the arcade, significantly lower central foveal thickness (CFT), reduced scotopic and phot...

Inherited epidermolysis bullosa (EB) comprises a group of genetic disorderscharacterized by fragile skin that blisters easily. Targeted therapies for EB necessitatepersonalized approaches, underscoring the importance of precise diagnostics throughgenetic analysis and skin biopsy using transmission electron microscopy and/or immuno-histochemistry. T...

Cadmium (Cd) is a toxic heavy metal that poses significant threats to wheat production and productivity, leading to stunted growth, discolored leaves, and diminished biomass and yield. Therefore, identification of Cd tolerance quantitative trait loci (QTL) in wheat is crucial for breeding Cd tolerant wheat, thereby ensuring stable and productive yi...

Mucopolysaccharidosis IV-A (MPS IV-A) is an autosomal recessive genetic disorder caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase, leading to the accumulation of chondroitin-6-sulfate (C6S) and keratan sulfate (KS). This is a rare disease, and, in Colombia, it is classified as an orphan disease under Resolution 023 of 2023. No...

Existing approaches to identifying cancer genes rely overwhelmingly on DNA sequencing data. Here, we introduce RVdriver, a computational tool that leverages paired bulk genomic and transcriptomic data to classify RNA variant allele frequencies (VAFs) of non-synonymous mutations relative to a synonymous mutation background. We analyze 7882 paired ex...

Retinitis Pigmentosa (RP) refers to a group of inherited retinal disease, often leading to legal and sometimes complete blindness. It is estimated that over a million people are afflicted with RP all over the world and show tremendous genetic and phenotypic heterogeneity, involving over 90 genes in its causation. The present literature review inten...

TP53 is included in most cancer predisposition multigene panels, especially those exploring Hereditary Breast and Ovarian Cancer (HBOC) predisposition. The purpose of this study was to define the contribution of TP53 pathogenic variants (PV) to the HBOC phenotype by collecting genotypes and phenotypes of 398 patients harboring a TP53 variant identi...

Citation: Kulibaba, R.O.; Srikulnath, K.; Singchat, W.; Liashenko, Y.V.; Griffin, D.K.; Romanov, M.N. The Application of Microsatellite Markers as Molecular Tools for Studying Genomic Variability in Vertebrate Populations. Curr. Issues Mol. Biol. 2025, 47, 447. https://doi. Abstract: Vertebrate molecular genetic research methods typically employ si...

Introduction WT1 -related disorders are associated with WT1 gene variants. Recent advances in genetic medicine have led to a better understanding of the genotype–phenotype correlation in WT1 -related diseases, particularly missense variants in exons 8 or 9 that lead to a wide range of severities. Exonic variants can lead to splicing abnormalities i...

Introduction Wilson’s disease (hepatolenticular degeneration) is a common hereditary neurological disorder. Early diagnosis, particularly the widespread implementation of genetic testing and timely intervention, is crucial for improving the prognosis of this disease. However, limited data exist on genotype-phenotype correlations, thereby impeding a...

Abstract: Stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is a devastating disease that threatens wheat production globally. The ability of Pgt to rapidly evolve new virulent races makes it one of the most challenging biotrophic fungal pathogen of wheat. Developing resistant wheat varieties is crucial, as genetic resistance provides a...

Inherited retinal diseases (IRDs) are rare disorders, typically presenting as Mendelian traits, that result in stationary or progressive visual impairment. They are characterized by extensive genetic heterogeneity, possibly the highest among all human genetic diseases, as well as diverse inheritance patterns. Despite advances in gene discovery, lim...

In this study, we characterized a panel of 1264 maize near‐isogenic lines (NILs), developed from crosses between 18 diverse inbred lines and the recurrent parent B73, referred to as nested NILs (nNILs). In this study, 888 of the nNILs were genotyped using genotyping‐by‐sequencing (GBS). Subsequently, 24 of these nNILs, and all the parental lines, w...

Phenylketonuria (PKU) is the most common inborn disorder of amino acid metabolism caused by biallelic pathogenic variants in phenylalanine hydroxylase (PAH) gene. This study comprised genomic profiling and phenotypic characterization of 131 Serbian PKU patients along with implications for BH4 therapy. By combining Sanger sequencing, MLPA and WES re...

Introduction Tooth agenesis (TA) is a common craniofacial malformation in humans, characterized by the absence of one or more permanent teeth. Recent studies have identified the low-density lipoprotein receptor-related protein 6 (LRP6) gene as an autosomal dominant contributor to TA. Herein we aimed to identify novel LRP6 variants in patients with...

Sarpagan and akuammiline monoterpenoid indole alkaloids (MIAs) are a class of bioactive plant‐derived compounds with significant pharmaceutical potential. These alkaloids are formed through oxidative cyclization of geissoschizine, catalyzed by homologous cytochrome P450 monooxygenases (CYP) known as sarpagan bridge enzymes (SBEs) and rhazimal synth...

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we ident...

Integrating, learning from, and predicting using vast datasets from various scales, platforms, and species is crucial for advancing crop improvement through breeding. Artificial intelligence (AI) is a broad category of methods, many of which have been used in breeding for decades. Recent years have seen an explosion of new AI tools (or old ones at...

Schistosomiasis remains a major global public health challenge. Bulinus serves as an intermediate host for Schistosoma, including S. haematobium, S. intercalatum, and S. guineensis. Emerging evidence suggests that temperature fluctuations associated with global climate change are key factors influencing the survival and distribution of Bulinus. The...

As sequencing technologies advance and costs decline, there has been a surge in the application of RNA sequencing (RNA-seq) in understanding biological processes. In addition to the typical uses of RNA-seq for transcriptomics, gene annotation, novel gene discovery, and network analysis, these data can enable a deeper understanding of cellular proce...

Background and Objectives Alexander disease is a rare monogenic disorder caused by dominant variants in GFAP (glial fibrillary acidic protein). Over 180 variants have been associated with the disease, with a wide spectrum of severity and clinical manifestations. Previous attempts at genotype-phenotype correlations have been hampered by the small nu...

Purpose Facial dysmorphism is a feature of many monogenic disorders, and is important in diagnostics, variant interpretation and nosology. Nevertheless, comprehensively assessing the complex facial shape changes associated with specific syndromes remains challenging. Here, we present 3D morphometric approaches to overcome these limitations, utilizi...

Globally, tuberculosis (TB) remains a top cause of death from infectious diseases, with an estimated 1.5 million deaths annually. Given its substantial social and economic burden, TB is a priority in the United Nations 2030 Agenda for Sustainable Development. The WHO's End TB Strategy emphasises research, innovation, and the rapid implementation of...

Background: Lipoid congenital adrenal hyperplasia (LCAH) is the lethal form of steroid biosynthesis defects because of mutations in the steroidogenic acute regulatory (STAR) gene. There are two distinct clinical forms including classical and nonclassical without any reliable genotype–phenotype correlation, and investigation of more cases may provid...

Background Pathogenic variants in QARS1 (MIM:603727; Glutaminyl-TRNA Synthetase 1), which encodes Glutaminyl-tRNA synthetase 1, have been associated with rare progressive microcephaly with seizures and cerebral and cerebellar atrophy (MSCCA MIM:615760). Only a handful of MSCCA patients have been reported in the literature mostly associated with com...

Introduction In this retrospective study, we analyzed clinical, biochemical, and genetic data and examined correlations between prevalent variants and outcomes of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Methods Patients with VLCAD deficiency confirmed through molecular genetic testing at King Saud Medical City, Riyadh, Saudi Ara...

The rapid increase in greenhouse gases has accelerated global warming, causing significant issues related to climate change, biodiversity and agriculture and adversely affecting crop production and food supply. The molecular and physiological mechanisms by which plants respond to abiotic stresses such as drought, cold and heat are well understood,...

SATB2-associated syndrome is an autosomal dominant neurodevelopmental syndrome caused by genetic alterations in the transcription factor SATB2. The associated phenotype is variable, and genotype-phenotype correlation studies have not yet been able to explain differences in severity and symptoms across affected individuals. While haploinsufficiency...

Background Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the key enzyme initiating protein O - and N -glycosylation at the postsynaptic membrane. Variants in GFPT1 gene cause congenital myasthenic (GFPT1-CMS). However, the understanding of the phenotype and genetic spectrum of GFPT1-CMS remains limited. Methods A total of 24 patients wi...

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a rising prevalence, driven by multifactorial genetic and environmental factors. Among the genetic contributors identified, SCN2A, a critical gene encoding the Nav1.2 sodium channel, has been implicated in ASD and other related neurological conditions. This sy...

Phage therapy is emerging as a promising strategy against the growing threat of antimicrobial resistance, yet phage and bacteria are incredibly diverse and idiosyncratic in their interactions with one another. Clinical applications of phage therapy often rely on a process of manually screening collections of naturally occurring phages for activity...

Essential tremor (ET) is a common movement disorder, but its pathophysiologic mechanisms remain elusive. So far, a few genes/loci have been identified, but because of genetic heterogeneity, the genetic etiology of ET is still one of the main challenges. In this study, we report an autosomal dominant ET Chinese pedigree in which the patients present...

This case report and literature review documents an ultra-rare de novo copy number gain at 5q14.3q15. The patient’s phenotype included hypotonia, microcephaly, global developmental delay, iris hypoplasia, atrophy, sweat dysregulation, and skeletal implications, including camptodactyly. This case presentation provides novel insights into the genotyp...

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumor syndrome caused by inactivating mutations of the MEN1 gene and characterized by the occurrence of multiple endocrine tumors within a single patient (i.e., parathyroid, pituitary, and pancreatic neuroendocrine tumors (NETs)). However, the lack of a genotype–phenotype correlation d...

Andrographolide is a prominent labdane diterpenoid extracted from Andrographis paniculata with exceptional anti‐inflammatory properties. Commercial production of andrographolide relies exclusively on extraction from plant resources. Although the scaffold of andrographolide ent‐copalol has previously been biosynthesized, further oxidative modificati...

Background To identify the genetic variants underlying neurofibromatosis type 1 (NF1) and to investigate genotype-phenotype correlations. Methods Thirty-three patients from 27 Chinese pedigrees with suspected NF1 phenotypes underwent genetic analysis. The impact of splicing variant on NF1 mRNA processing was determined by cDNA direct sequencing. A...

Goitrous hypothyroidism, characterized by thyroid enlargement and impaired hormone production, arises from diverse genetic mutations affecting thyroid development and function. Advances in genetic analysis have expanded understanding of its molecular underpinnings, aiding early diagnosis and tailored interventions. Mutations in TG, TPO, DUOXA2, an...

Hidradenitis suppurativa and Dowling-Degos disease are two independent rare diseases with characteristic clinical manifestations. The PSENEN gene encodes a critical subunit of the γ-secretase complex, mutations of which can independently or concurrently lead to hidradenitis suppurativa and Dowling-Degos disease. Given the rarity of pathogenic PSENE...

Background Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) and primary ovarian insufficiency (POI) secondary to ovarian dysgenesis. However, the mutation spectrum of disease-causing genes for Perrault syndrome in the Chinese population remains poorly understood. In this study, we report on...

Purpose The aim of the study was to investigate genotype–phenotype correlations in Usher syndrome (USH). Method Thirty-five USH patients were included, categorized into three genetic-based groups: USH1 (n = 11), USH2 (n = 22), and USH4 (n = 2). The functional and emotional impact of dizziness and equilibrium was assessed using the Dizziness Handic...

Background Spectrins are ubiquitous cytoskeleton proteins found in all metazoan cells. αII-spectrin, encoded by SPTAN1, is the pivotal protein responsible for organization of the axonal cytoskeleton. Monoallelic SPTAN1 mutations cause various inherited neurological diseases, including spastic paraplegia 91 (SPG91), a type of hereditary spastic para...

Purpose This study aimed to identify the genetic variants associated with early embryonic developmental arrest (EDA) in infertile patients and to expand the genotypic and phenotypic spectrum of maternal-effect genes, including PATL2, WEE2, and TUBB8, which are critical for oocyte maturation arrest (OMA) and fertilization failure (FF) as previously...

The GenIDA project aims to improve the understanding and management of rare genetic forms of intellectual disability by fostering collaboration among patients, caregivers, healthcare professionals, and research professionals. Clinical data is provided by patients’ families via a structured questionnaire to identify medically relevant insights and b...

Introduction Deepening the genetic mechanisms underlying Normal Hearing Function (NHF) has proven challenging, despite extensive efforts through Genome-Wide Association Studies (GWAS). Methods NHF was described as a set of nine quantitative traits (i.e., hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and three pure-tone averages of threshold...

Rice serves as the primary food source for over half the world's population, making its stable production is critical for global food security. The brown planthopper (BPH, Nilaparvata lugens Stål.) ranks among the most devastating rice pests worldwide. Developing BPH-resistant varieties through resistance gene discovery represents the most sustaina...

In the present study, an exceptional germline gene fusion involving the protein-coding MN1 gene and the long non-coding RNA (lncRNA) gene CPMER was detected as the genetic cause of severe cerebral abnormalities with unfavorable prognosis in a male fetus at 14 weeks of gestation. Quantitative and qualitative RNA analyses indicate the expression of C...

Purpose Congenital hyperinsulinism (CHI) represents the most frequent cause of recurrent hypoglycemia in neonates and infants, stemming from defects in the regulatory pathways of insulin secretion from pancreatic beta cells. This study aims to assess the clinical and genetic characteristics of a CHI cohort and to discuss the complexities involved i...

Protein-level cellular dynamics, including multimerization, play a crucial role in rapid adaptation of plants during developmental transitions and environmental stresses. The gaseous hormone ethylene is a key regulator of these rapid cellular adjustments, especially in growth inhibition. During soil emergence, etiolated seedlings undergo crucial mo...

Tooth agenesis is among the most prevalent congenital anomalies affecting human dentition, characterized by the developmental absence of one or more teeth. This condition may be present in either syndromic or non-syndromic forms, with significant implications for oral function, aesthetics, and craniofacial development. This narrative review aims to...

DOI: https://www.doi.org/10.33545/26174693.2025.v9.i5Sa.4300 Abstract Crop improvement is pivotal to addressing the global challenges of food security and sustainable agriculture amid climate change and population growth. Advances in genomics and proteomics have revolutionized traditional breeding, enabling detailed dissection of the molecular mech...

Objective Recently, a mitochondrial encephalopathy due to biallelic HPDL variants was described, associated with a broad range of clinical manifestations ranging from severe, infantile‐onset neurodegeneration to adolescence‐onset hereditary spastic paraplegia. HPDL converts 4‐hydroxyphenylpyruvate acid (4‐HPPA) into 4‐hydroxymandelate (4‐HMA), nece...

Goitrous hypothyroidism, characterized by thyroid enlargement and impaired hormone production, arises from diverse genetic mutations affecting thyroid development and function. • Advances in genetic analysis have expanded understanding of its molecular underpinnings, aiding early diagnosis and tailored interventions. A systematic review of studies...

Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive, progressive, multisystem hereditary lysosomal storage disease (LSD), which is characterized by the gradual accumulation of dermatan sulphate (DS), heparan sulphate (HS), and glycosaminoglycans (GAGs) in all organs and tissues due to the deficiency of the enzyme α-L-hyduronidase. The mu...

Harmonized phenotyping and diverse population-specific studies are crucial for advancing gene discovery in psychiatric genetics. We conducted a genome-wide association (GWAS) mega-analysis of DSM-defined lifetime major depressive disorder (MDD) in 64 941 participants (25.7% cases) from the Dutch BIObanks Netherlands Internet Collaboration (BIONIC)...

Increasing the genomic resources of emerging aquaculture crop targets can expedite breeding processes as seen in molecular breeding advances in agriculture. High quality annotated reference genomes are essential to implement this relatively new molecular breeding scheme and benefit research areas such as population genetics, gene discovery, and gen...

Phelan–McDermid syndrome (PMS; #MIM: 606232) is a rare neurodevelopmental disorder primarily caused by the haploinsufficiency of the SHANK3 gene, most often due to deletions encompassing the gene or single nucleotide variants within it. Individuals with PMS display a wide range of clinical abnormalities and considerable genetic heterogeneity. This...

Background To understand the pathogenetic mechanisms shared among schizophrenia (SCZ), bipolar disorder (BP), and major depression (MDD), we investigated the pleiotropic mechanisms using large-scale genome-wide and brain transcriptomic data. Methods We analyzed SCZ, BP, and MDD genome-wide association datasets available from the Psychiatric Genomi...

Sjögren’s disease (SjD) is a systemic autoimmune disorder primarily causing dry eyes and mouth. It frequently overlaps with other autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic basis of SjD remains underexplored, limiting our understanding of its connections to other immu...

Familial adenomatous polyposis (FAP) is the most common hereditary colorectal adenomatous polyposis and cancer syndrome which has historically been associated with a near absolute risk of colorectal cancer. However, the morbidity and mortality from colorectal cancer has been greatly diminished by pre-symptomatic genetic testing which identifies aff...

Background/Objectives: Pathogenic variants in the growth differentiation factor 2 (GDF2) gene have been linked to a hereditary hemorrhagic telangiectasia (HHT)-like syndrome, yet their clinical significance remains under investigation. This study reports seven pediatric patients with GDF2 variants from a single center. Methods: We identified childr...

Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by high levels of low-density lipoprotein (LDL). This study aimed to identify variants in the LDLR, APOB, PCSK9 and LDLRAP1 genes and to identify the genotype–phenotype correlation in Serbian FH patients. Method: This study included a...

Background and Objectives: Poretti–Boltshauser syndrome (PBS) is a rare, autosomal recessive disorder caused by pathogenic variants in the LAMA1 gene, resulting in laminin dysfunction. This manifests as a cerebellar malformation with cysts, and patients present with developmental delay and ataxia; however, ocular features are not well-characterised...

Background The microtubule actin crosslinking factor 1 ( MACF1) gene encodes microtubule–microfilament cross-linking factor 1 that plays an essential role in the embryonic brain development. MACF1 variants were associated with lissencephaly-9 (LIS9). However, the MACF1 -epilepsy relationship was unknown. Methods Trios-based whole-exome sequencing...

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor accounting for less than 5% of all thyroid cancers. An estimated 25% of cases are familial secondary to a germline mutation on the rearranged during transfection proto-oncogene ( RET ); this gene can be present as a somatic mutation in approximately 40%–60% of sporadic MTC tumors. The...

Townes-Brocks syndrome (TBS, MIM#107480) is an autosomal dominant disorder linked to SALL1 alterations and characterized by a clinical triad (anorectal, thumb, and external-ear malformations), along with variable features. Renal failure and deafness can occur at any age, making follow-up essential. Some genotype-phenotype correlations have been sug...

Glycogen storage diseases (GSDs) are a group of inherited disorders caused by genetic defects in various enzymes involved in glycogen production or breakdown. Hepatic GSDs often have overlapping clinical features, making subtyping or prognostication difficult. With the availability and advancement of next-generation sequencing, definitive molecular...

Despite the extensive use of biomarkers like PSA, AMACR, and PCA3, prostate cancer (PCa) is still a major clinical challenge, demanding the development of more precise and specific methods for diagnosis. In this study, a deep learning model was applied to identify ten key genes from a pool of 68 common differentially expressed genes in the three tr...

Background Patients with Hermansky-Pudlak syndrome (HPS) typically present with a triad comprising tyrosinase-positive oculocutaneous albinism, a tendency to bleed easily, and ceroid accumulation in multiple tissues. Ocular findings in patients with HPS include poor vision, refractive errors, photophobia, periodic alternating nystagmus, iris transi...

Bullous pemphigoid (BP) is a rare autoimmune disease, primarily affecting elderly individuals, that significantly impacts the patient’s quality of life. In contrast, psoriasis vulgaris (PV) is a common, chronic, immune-mediated skin condition recognized as a systemic T-cell-mediated disorder. We aim to present the case of a patient suffering from a...

Spatial transcriptomics (ST) combines single-cell RNA-seq gene expression data with spatial coordinates to provide an accurate, 2D picture of gene expression across a tissue sample. With this technology, we can discover detailed RNA localization, study development, investigate the tumor microenvironment, and create a tissue atlas. Full ST analysis...

Mammals utilize imprinted and X-linked epigenetic mechanisms in development, metabolism, and behavior. Imprinted genes, including Prader-Willi syndrome Snord116 noncoding RNAs, are implicated in the regulation of sleep and circadian rhythms through poorly understood mechanisms. Utilizing mouse models of Snord116 deficiency and overexpression, we pe...

Hereditary spherocytosis (HS) is a common form of haemolytic anaemia caused by defects or deficiencies in genes encoding erythrocyte membrane proteins, such as ANK1, SPTB, SLC4A1, EPB42, and SPTA1. Among these, ANK1 and SPTB mutations are the most frequent causes of HS worldwide. This study analysed 53 Indian HS patients, identifying 33 novel and 1...