During a routine test, we identified a 38-year-old man who had a positive hematology screening result but was negative for hot spot variants of his thalassemia gene. Further analysis identified β–50 (HBB: c.-100G>A). It was first suggested that β–50 was a β+-thal allele, and some research groups suggested this allele was a silent β-thal allele. To fully understand the hematological phenotype of the

Although imputation of missing SNP results has been widely used in genetic studies, claims about the quality and usefulness of imputation have outnumbered the few studies that have questioned its limitations. But it is becoming clear that these limitations are real—for example, disease association signals can be missed in regions of LD breakdown. Here, as a case study, using the chromosomal region

In this study, we aimed to investigate the relationship between the genetic variant of rs696217-ghrelin and fasted lipid profile, indices of obesity, and environmental parameters. Amplification refractory mutation system-polymerase chain reaction (ARMs-PCR) was used for genotyping 1118 individuals recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The

PRUNE1 is linked to a wide range of neurodevelopmental and neurodegenerative phenotypes. Multiple pathogenic missense and stop-gain PRUNE1 variants were identified in its DHH and DHHA2 phosphodiesterase domains. Conversely, a single splice alteration was previously reported. We investigated five patients from two unrelated consanguineous Sudanese families with an inherited severe neurodevelopmental

The study was conducted between 2018 and 2020. From a cohort of 113 hearing impaired (HI), five non-DFNB12 probands identified with heterozygous CDH23 variants were subjected to exome analysis. This resolved the etiology of hearing loss (HL) in four South Indian assortative mating families.

Great efforts have been made on the algorithms that deal with RNA-seq data to enhance the accuracy and efficiency of differential expression (DE) analysis. However, no consensus has been reached on the proper threshold values of fold change and adjusted p-value for filtering differentially expressed genes (DEGs). It is generally believed that the more stringent the filtering threshold, the more reliable

In the early 2000s, emerging SARS-CoV-2, which is highly pathogenic, posed a great threat to public health. During COVID-19, epigenetic regulation is deemed to be an important part of the pathophysiology and illness severity. Using the Illumina Infinium Methylation EPIC BeadChip (850 K), we investigated genome-wide differences in DNA methylation between healthy subjects and COVID-19 patients with different

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic predisposition. Genome-wide association studies (GWAS) of SLE have identified more than 50 robust susceptibility loci. However, traditional individual SNP-based GWAS have made it difficult to identify variants with small effects. Moreover, variants revealed by GWAS only explain a limited disease heritability, suggesting

Bone mineral density (BMD) and whole-body lean mass (WBLM) are two important phenotypes of osteoporosis and sarcopenia. Previous studies have shown that BMD and lean mass were phenotypically and genetically correlated. To identify the novel common genetic factors shared between BMD and WBLM, we performed the conditional false discovery rate (cFDR) analysis using summary data of the genome-wide association

Brain malformations have been reported in RASopathies, including postnatal external hydrocephalus, a nonobstructive form of cerebrospinal fluid accumulation around the brain. It was described in a few patients with mutations of other genes than PTPN11, such as SOS1 and SHOC2 and never in prenatal diagnosis. The aim of this case report is to describe the prenatal presentation of a fetus with Noonan

Ring finger protein 213 (RNF213) is a susceptibility gene of moyamoya disease (MMD). A previous case–control study and a family analysis demonstrated a strong association of the East Asian-specific variant, R4810K (rs112735431), with MMD. Our aim is to uncover evolutionary history of R4810K in East Asian populations.

Hereditary myopathies are a heterogeneous disorder known to be associated with more than 100 genes. Although hereditary myopathy subgroups can be partially described with traditional methods such as muscle biopsy, next-generation sequencing (NGS) is essential to reveal the disease's underlying genetic etiology and molecular mechanisms. In this study, we performed clinical exome sequencing or whole-exome

Protein kinase C theta (PKCθ) is expressed in ER‐negative breast cancer and promotes cancer stem cells (CSCs) phenotype. PKCθ gene (PRKCQ) is predicted to be a target for tumor suppressor miR‐203. Herein, we aim to validate this prediction and evaluate the ability of miR‐203 to inhibit migration of breast cancer cell line enriched with CSCs, MDA‐MB‐231, via PRKCQ targeting.

Lung adenocarcinoma (LUAD) is one of the most common forms of lung cancer, with a very high mortality rate. Although the treatments available for LUAD have become more effective in recent years, significant improvement is still needed. Advances in sequencing technologies and bioinformatics analysis have enabled new approaches to be developed for identifying drug targets. In this work we utilized data

Abnormalities in the normal left–right axis asymmetry range from situs inversus totalis to situs ambiguous or heterotaxy. More than 80 genes have been described to have a role in the establishment of the normal situs of the internal organs. Pathogenic variants in the PKD1L1 gene have recently been described in heterotaxy and congenital heart disease. Till date, 11 families have been described with

Alopecia-mental retardation syndrome (APMR) is a rare autosomal recessive neuro-dermal disorder. It is characterized by heterogeneous phenotypic features, that is, absence of hair on the scalp, eyelashes, and eyebrows and mild to severe intellectual disability. So far, approximately 14 families (i.e., Iranian, Pakistani, and Swiss) with APMR have been reported in the scientific literature. Its precise

To investigate the variant spectrum and genotype–phenotype correlations in a Turkish cohort with Neurofibromatosis Type-1 (NF1).

Population stratification (PS) is a confounding factor in genome‐wide association studies (GWASs) and also an interesting process itself. Latin American populations have mixed genetic ancestry, which may account for PS. We have analyzed the relatedness, by means of the identity‐by‐descent (IBD) estimations, in a sample of 1805 individuals and 1.006.703 autosomal mutations from a case–control study

With the emergence of modern genetic testing and profiling techniques, it has become imperative to assess the general public awareness and attitudes toward such developments. The public's perspective and possible responses are necessary for planning commercial, legal, medical, or healthcare initiatives. The purpose of this study was to assess the perception of the general public and professionals about

On behalf of the Annals of Human Genetics (The Annals), we would like to reinforce the fact that this journal offers fair and rigorous editorial evaluation of all original research submissions. After the initial editorial evaluation, a manuscript will either be returned to the author with comments or it will be sent for external peer‐review to at least two anonymous reviewers, for rigorous scientific

β‐thalassemia (β‐thal) (3.5 kb deletion or NC_000011.10:g.5224302‐5227791del3490bp) is a common mutation in southern Thailand. This study aimed to determine genetic diversity in subjects with β‐thal (3.5 kb deletion) alleles and to ascertain the origin of this mutation using haplotype and phylogenetic analysis. The study was carried out on members of the southern Thai population, including 45 normal

A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine

Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)-mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole-exome sequencing of 50 DNA samples from a healthy Korean population revealed a total

Various somatic isocitrate dehydrogenase 1 (IDH1) gene variants have been reported to drive lower-grade gliomas and secondary glioblastomas. In the current study, we explored the IDH1 variants in the glioma biopsy samples of patients from Pakistan. We explored the incidence of isocitrate dehydrogenase 1 gene variants by hotspot sequencing in 80 formalin-fixed paraffin-embedded tissues of different

OBJECTIVE To assess the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS) to further delineate the fetal presentation of this syndrome. METHODS This was a retrospective study. Fetal MDS was diagnosed prenatally by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal characteristics, indications for prenatal diagnosis, sonographic findings, CMA

Osteoporosis is a common skeletal disorder characterized by deterioration of bone tissue. The set of genetic factors contributing to osteoporosis is not completely specified. High-risk osteoporosis pedigrees were analyzed to identify genes that may confer susceptibility to disease. Candidate predisposition variants were identified initially by whole exome sequencing of affected-relative pairs, approximately

Type 1 diabetes (T1D) is a chronic autoimmune disease with a complex interrelation of genetic and environmental factors. Genetic studies have reported HLA and non-HLA loci as significant contributors to T1D. However, the genetic basis of T1D among Emiratis is unexplored. This study aims to determine the contribution of four genes PTPN22, CTLA-4, IL2-RA, and INS to T1D risk among Emiratis. The association

Structural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants, and accurate genotyping of this complex structural variation

Familial Mediterranean fever (FMF) is a recessive autoinflammatory disease, mainly occurring in the eastern Mediterranean. In these populations, the five FMF founder mutations are differently distributed. In Algeria, the FMF‐causing variants remain poorly explored. This retrospective study aims to report the mutational profile of Algerian FMF patients and to compare it with North African FMF patients

Variants perturbing the normal splicing of pre‐mRNA can lead to human diseases. The splice‐altering effect and eventual consequence on gene function was sometimes uncertain and hinders a definitive molecular diagnosis.

Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI‐specific genes and correlate these with phenotypes

Mosaic segmental and whole chromosome copy number alterations are postzygotic variations known to be associated with several disorders. We have previously presented an efficient targeted sequencing approach to simultaneously detect point mutations and copy number variations (CNVs). In this study, we evaluated the efficiency of this approach to detect mosaic CNVs, using seven postnatal and 19 tumor

Osteogenesis imperfecta (OI), also known as “brittle bone disease,” is a rare inherited genetic disorder characterized by bone fragility and often associated with short stature. The mutation in WNT1 causes autosomal recessive OI (AR‐OI) due to the key role of WNT/β‐catenin signaling in bone formation. WNT1 mutations cause phenotypes in OI of varying degrees of clinical severity, ranging from moderate

Bardet–Biedl syndrome (BBS) is a very‐rare autosomal recessive genetic disorder with severe multisystem manifestations. Genetic testing plays an important role in the early diagnosis of the disease. In this study, while trying to elucidate the genetic etiology of seven individuals with clinical BBS diagnosis from six different families, we also aimed to examine the distribution of BBS variations in

Recently, NCAPH (non‐SMC condensin I complex subunit H), a regulatory subunit of the condensin complex, has captured our attention in various cancer studies. However, the function of NCAPH in endometrial cancer (EC) remains unclear. Our study aims to investigate the role of NCAPH in EC.

Currently, next‐generation sequencing (NGS) technology is more accessible and available to detect the genetic causation of diseases. Though NGS technology benefited some clinical phenotypes, for some clinical diagnoses such as seizures and epileptic disorders, adaptation occurred slowly. The genetic diagnosis was mainly based on epilepsy gene panels and not on whole exome and/or genome sequencing.

The complexity in the molecular diagnosis of Cystic Fibrosis (CF) also depends on the variable prevalence/incidence of the disease associated with the wide CFTR allelic heterogeneity among different populations. In fact, CF incidence in Asian and African countries is underestimated and the few patients reported so far have rare or unique CFTR pathogenic variants. To obtain insights into CF variants

The consumer genomics industry is steadily growing and delivering genetic information to over 10 million individuals. Yet, the implications of using data from different services remain unclear. We investigated the genotyped sites, concordance, and genetic risk estimation using data from three consumer services—two single nucleotide polymorphism (SNP)‐array based and one sequencing based. In an N‐of‐one

We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically

BACKGROUND Familial Mediterranean fever is a hereditary inflammatory disorder caused by variants in MEFV. c.2230G>T p.(Ala744Ser) rs61732874 is considered to be an established pathogenic variant in MEFV, but in this study we provide a complete evaluation that suggests this variant is likely benign. METHODS Using an in-house exome database from 924 individuals, we extracted all individuals harboring

The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein-coding variants were studied, including three novel variants (L22V, R287T, and G410C) and three previously reported variants (R36S, Q259K

The aim was to examine the association between the hypoxia-inducible factor-1α (HIF1A) gene and the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene polymorphisms and the endurance/power athlete status and relative aerobic capacity. Another goal of this study was to reveal the connection between GNB3, blood pressure (BP), body composition and body mass index (BMI). Two hundred thirty-eight

Perrault syndrome is a rare disorder characterized by ovarian dysgenesis, bilateral sensorineural hearing loss and associated with mutations in six mitochondrial proteins. Additional neurological features were also described. Herein, we report on a 27-year-old woman with Perrault syndrome (PS), moderate ataxia and axonal sensory-motor peripheral neuropathy in whom we identified compound heterozygous

The UK Biobank is an unprecedented resource for human disease research. In March 2019, 49,997 exomes were made publicly available to investigators. Here we note that thousands of variant calls are unexpectedly absent from this dataset, with 641 genes showing zero variation. We show that the reason for this was an erroneous read alignment to the GRCh38 reference. The missing variants can be recovered

PTEN gene mutations are responsible for the PTEN hamartoma tumor syndrome (PHTS). In this study, clinical and molecular findings of patients carrying PTEN mutations are presented. Our aim is to contribute to genotype–phenotype correlation and define the most common findings of the syndrome in pediatric patients.

The present study aimed to perform chromosome examination and pedigree analysis on three patients with semen abnormality who had undergone in vitro fertilization–embryo transfer (IVF‐ET). Peripheral blood cell culture and chromosome karyotyping were performed on 4,200 individuals who had undergone chromosome examination. Among them, 155 pregnant women who had successfully conceived were subjected to

Leigh syndrome is a clinically and radiologically heterogeneous condition with approximately 75 genes, nuclear and mitochondrial, known to be implicated in its pathogenesis. Leigh syndrome due to complex II deficiency constitutes 2% to 7% of these cases. Previously, nine individuals with Leigh syndrome have been reported with pathogenic variants in SDHB, which encodes for the iron–sulfur cluster subunit

Oculocutaneous albinism (OCA) is a group of congenital autosomal recessive disorders with seven known subtypes (OCA1–OCA7) characterized by loss or absence of pigmentation in the skin, hair, and eyes. OCA1, caused by pathogenic variations in the tyrosinase (TYR) gene, has been documented to be the most prevalent subtype across the world including India. In the present study, we recruited 53 OCA‐affected

PURPOSE Laotians and Lao Isan are widely spread Lao groups who live in Laos and northeastern Thailand, respectively. We explored the genetic structure between them and other ethnic groups from Thailand to clarify historical patterns of admixture between Tai-Kadai and Austroasiatic speakers, and to expand the forensic reference database for the region. SUBJECTS AND METHODS We combined new genetic data

The original name of the Annals of Human Genetics was the Annals of Eugenics and the early contributors to the journal had a historical involvement with what was to become the eugenics movement. In this context, the Annals bears a special responsibility to promote the highest ethical standards and to look closely at its own role as a publisher of genetics research. This may extend beyond complying

The human dopamine transporter (hDAT) participates in dopamine homeostasis by clearing dopamine from the extracellular space using secondary active transport. Dysregulation of hDAT has been reported to be associated with different neuropsychiatric disorders. Dopamine transporter deficiency syndrome (DTDS) is a complex disease caused by defects in dopamine uptake within the synaptic cleft and patients

Previous studies have implicated common and rare genetic variants as risk factors for late‐onset Alzheimer's disease (LOAD). Here, weighted burden analysis was applied to over 10,000 exome‐sequenced subjects from the Alzheimer's Disease Sequencing Project. Analyses were carried out to investigate whether rare variants predicted to have a functional effect within a gene were more commonly seen in cases

OBJECTIVE Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver diseases. However, the pathogenesis of NAFLD is largely unknown. Here, we investigated the specific role of miR-499-5p in NAFLD. METHODS Free fatty acid was used to induce HL-7702 cell line to establish a NAFLD cell model, and animal models of NAFLD were constructed by feeding C57BL/6 mice with a high-fat

The linkage disequilibrium (LD) score regression method tests whether there is an association between the LD score and allele frequency differences between cases and controls. It makes the assumption that there is no association between LD score and allele frequency differences among populations and hence that any observed association is the result of a polygenic effect rather than population stratification