Search Our Scientific Publications & Authors

Ann Hum Genet 2022 May 18. Epub 2022 May 18.

School of Statistics, Capital University of Economics and Business, Beijing, China.

One of the critical issues in genetic association studies is to evaluate the risk of a disease associated with gene-gene or gene-environment interactions. The commonly employed procedures are derived by assigning a particular set of scores to genotypes. However, the underlying genetic models of inheritance are rarely known in practice. Read More

Ann Hum Genet 2022 May 16. Epub 2022 May 16.

Department of Psychological Sciences & Brain Health Research Institute, Kent State University, Kent, Ohio, USA.

Despite the robustness of DRD4 polymorphism associations with brain-based behavioral characteristics in candidate gene research, investigations have minimally explored associations between these polymorphisms and emotional responses. In particular, the prevalent single nucleotide polymorphism (SNP) -521C/T (rs1800955) in the promoter region of DRD4 remains unexplored relative to emotions. Here, two independent samples were evaluated using different emotion elicitation tasks involving social stimuli: Study 1 (N = 120) evoked positive and negative emotional responses to validated film clips; Study 2 (N = 122) utilized Cyberball to simulate social rejection and acceptance. Read More

Ann Hum Genet 2022 Apr 22. Epub 2022 Apr 22.

Department of Genetics, University of Delhi South Campus, New Delhi, India.

Primary microcephaly and Seckel syndrome are rare genetically and clinically heterogenous brain development disorders. Several exonic/splicing mutations are reported for these disorders to date, but ∼40% of all cases remain unexplained. We aimed to uncover the genetic correlate(s) in a family of multiple siblings with microcephaly. Read More

Ann Hum Genet 2022 Apr 18. Epub 2022 Apr 18.

School of Rehabilitation and Health Preservation, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)-CLOCK SNP rs1801260 and ADH4 SNPs rs1800759, and rs1126671-with CH were studied previously, but the results were inconsistent.

Methods: Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Read More

Ann Hum Genet 2022 Apr 8. Epub 2022 Apr 8.

Department of Preventive Medicine, School of Medicine, Shihezi University, Shihezi, Xinjiang, 832000, China.

Purpose: The polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T has been linked to H-type hypertension. But the conclusion remained controversial. To elucidate this issue, we performed a comprehensive meta-analysis to analyze the MTHFR C677T polymorphism and H-type hypertension. Read More

Ann Hum Genet 2022 Mar 31. Epub 2022 Mar 31.

Department of Anatomy and Anthropology, Tel Aviv University, Tel Aviv, Israel.

Metabolic syndrome (MetS) is diagnosed by the presence of high scores on three or more metabolic traits, including systolic and diastolic blood pressure (SBP, DBP), glucose and insulin levels, cholesterol and triglyceride (TG) levels, and central obesity. A diagnosis of MetS is associated with increased risk of cardiovascular disease and type 2 diabetes. The components of MetS have long been demonstrated to have substantial genetic components, but their genetic overlap is less well understood. Read More

Ann Hum Genet 2022 Mar 28. Epub 2022 Mar 28.

Laboratorios de Investigación en Biología Molecular e Inmunología. Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic, Nayarit, México.

Aim: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic condition in which both lifestyle and genetic factors have a pathogenic role. The LEP gene encodes leptin, which regulates appetite, body weight, and several metabolic functions. Proopiomelanocortin (POMC), regulates food intake and energy balance. Read More

Ann Hum Genet 2022 Mar 21. Epub 2022 Mar 21.

Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Ann Hum Genet 2022 Mar 16. Epub 2022 Mar 16.

College of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China.

Ann Hum Genet 2022 May 24;86(3):153-158. Epub 2022 Feb 24.

Department of Genetics, Evolution and Environment, University College London, London, UK.

Ann Hum Genet 2022 Feb 9. Epub 2022 Feb 9.

Inserm UMR 1231 GAD, Faculty of Health Sciences, University of Burgundy and Franche-Comté, Dijon, France.

It has been estimated that Copy Number Variants (CNVs) account for 10%-20% of patients affected by Developmental Disorder (DD)/Intellectual Disability (ID). Although array comparative genomic hybridization (array-CGH) represents the gold-standard for the detection of genomic imbalances, common Agilent array-CGH 4 × 180 kb arrays fail to detect CNVs smaller than 30 kb. Whole Exome sequencing (WES) is becoming the reference application for the detection of gene variants and makes it possible also to infer genomic imbalances at single exon resolution. Read More

Ann Hum Genet 2022 May 7;86(3):137-144. Epub 2022 Feb 7.

Research laboratory LR18/SP12 auto-immunity, cancer and immunogenetics, Immunology Department, Habib Bourguiba university Hospital, University of Sfax, Sfax, Tunisia.

Aim: Through their recognition of various bacterial cell wall components, TLR2 and TLR4 participate in the innate response and modulate the activation of adaptive immunity. Therefore, the genetic background of these receptors might play a crucial role in autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated the possible association between polymorphisms within TLR2 and TLR4 genes with SLE susceptibility. Read More

Ann Hum Genet 2022 Feb 3. Epub 2022 Feb 3.

Institut du Cerveau - Paris Brain Institute, ICM, Sorbonne Université, INSERM, CNRS, APHP, Paris, France.

Background: Intellectual disability is a form of neurodevelopmental disorders that begin in childhood and is characterized by substantial intellectual difficulties as well as difficulties in conceptual, social, and practical areas of living. Several genetic and nongenetic factors contribute to its development; however, its most severe forms are generally attributed to single-gene defects. High-throughput technologies and data sharing contributed to the diagnosis of hundreds of single-gene intellectual disability subtypes. Read More

Ann Hum Genet 2022 May 10;86(3):127-136. Epub 2022 Jan 10.

Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiao tong University, Xi'an, People's Republic of China.

Background: Rheumatoid arthritis (RA) is a complex disease with several risk factors. The effects of blood metabolites on RA remains elusive. We conducted a genetic correlation scan to explore the relevance of blood metabolism with RA. Read More

Ann Hum Genet 2022 May 28;86(3):119-126. Epub 2021 Dec 28.

Department of Medical Genetics, Ankara Numune Training and Research Hospital, Ankara, Turkey.

Progressive familial intrahepatic cholestasis (PFIC) is a rare genetically heterogeneous group of autosomal recessive liver disorders that manifests as intrahepatic cholestasis during the neonatal period. ATP8B1, ABCB11, and ABCB4 genes are responsible for PFIC type 1, PFIC type 2, and PFIC type 3, respectively. To determine the underlying molecular etiology of PFIC, 80 patients from 77 families were investigated. Read More

Ann Hum Genet 2022 May 20;86(3):109-118. Epub 2021 Dec 20.

Biochemistry Laboratory, La Paz University Hospital Health Research Institute (FIBHULP), IdiPAZ, Madrid, Spain.

Pathogenic variants in the AP4B1 gene lead to a rare form of hereditary spastic paraplegia (HSP) known as SPG47. We report on a patient with a clinical suspicion of complicated HSP of the lower limbs with intellectual disability, as well as a novel homozygous noncanonical splice site variant in the AP4B1 gene, in which the effect on splicing was validated by RNA analysis. We sequenced 152 genes associated with HSP using Next-Generation Sequencing (NGS). Read More

Ann Hum Genet 2022 03 13;86(2):102-107. Epub 2021 Dec 13.

Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Fluoropyrimidines are chemotherapy drugs that may cause severe adverse events, and their metabolism occurs by dihydropyrimidine deydrogenase (DPD), coded by DPYD. Variants in the DPYD were associated to a greater risk of toxicity. Our aim was to determine the frequency of the most relevant DPYD alleles according to CPIC guidelines (DPYD*2A-rs3918290, DPYD*13-rs55886062, rs67376798, and HapB3-rs75017182) in a sample of 800 healthy Southern Brazilians. Read More

Ann Hum Genet 2022 May 9;86(3):145-152. Epub 2021 Dec 9.

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, United Kingdom.

Alport syndrome is a genetic disorder affecting the basement membranes of the kidney, ear and eye, and represents a leading cause of monogenic kidney disease. Alport syndrome is genetically heterogeneous with three key genes involved (COL4A3-5) and several transmission patterns, including monogenic X-linked, autosomal recessive/dominant and digenic. We report a consanguineous family where 13 individuals presented variable features of Alport syndrome including kidney failure on two generations and male-to-male transmission, suggesting autosomal dominant inheritance. Read More

Ann Hum Genet 2022 03 9;86(2):80-86. Epub 2021 Dec 9.

Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon.

Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries with an incidence of 1:2500 in United States and 1:1000 in some European countries. Similar incidences were noted for the Middle East with variations from 1 in 2560 to 1 in 15,876 according to the degree of consanguinity. This is a preliminary systematic study that aims to assess the incidence and carrier rate of cystic fibrosis in the Middle Eastern Lebanese population; known for a high frequency of consanguinity. Read More

Ann Hum Genet 2022 03 8;86(2):94-101. Epub 2021 Dec 8.

Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.

TRAPPC4-related neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (MIM# 618741) is a recently described TRAPPopathy with clinical findings of developmental delay, seizures, postnatal microcephaly, spasticity, facial dysmorphism, and cerebral and cerebellar atrophy. Muscle involvement, a frequent finding in TRAPPopathies, was observed in one individual with TRAPPC4-related disorder previously. Only a single variant, an in-frame deletion in one family has been reported outside a recurrent disease-causing variant. Read More

Ann Hum Genet 2022 03 29;86(2):87-93. Epub 2021 Nov 29.

División de Genética. Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis (HS), and alpha thalassemia (α-thal) are frequent erythrocyte pathologies with different geographic distributions worldwide. Our aim is to report hematological and molecular findings of G6PD deficient Mexican patients in coinheritance with suggestive hereditary spherocytosis (sHS) and α-thal.

Methods: We studied 78 G6PD deficiency patients. Read More

Ann Hum Genet 2022 03 15;86(2):71-79. Epub 2021 Nov 15.

Department of Genetics & Molecular Medicine, Kamineni Hospitals, Hyderabad, Telangana, India.

Angelman syndrome (AS) (OMIM#105830) is an imprinting disorder caused due to alterations in the maternal chr 15q11-13 region. Majority of cases can be diagnosed by methylation-specific polymerase chain reaction (MS-PCR) of SNRPN gene and by UBE3A sequencing, however, about 10% of cases with AS phenotype remain undiagnosed. Differential diagnoses of AS can be detected by chromosomal microarray (CMA) and clinical exome sequencing (CES). Read More

Ann Hum Genet 2022 01 3;86(1):52-62. Epub 2021 Nov 3.

Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease caused by de novo pathogenic variants in YY1. In this study, we report a 10-year-old boy with a de novo novel pathogenic variant in YY1, the first Iranian patient with Gabriele-de Vries Syndrome.

Methods: The novel de novo pathogenic variant detected in this study (NM_003403:c. Read More

Ann Hum Genet 2022 01 28;86(1):45-51. Epub 2021 Sep 28.

RTI International, Research Triangle Park, North Carolina, USA.

The PhenX Toolkit (https://www.phenxtoolkit.org/) is an online catalog of recommended measurement protocols to facilitate cross-study analyses for biomedical research. Read More

Ann Hum Genet 2022 01 28;86(1):34-44. Epub 2021 Sep 28.

Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.

Ataxia telangiectasia (AT) is a rare autosomal recessive multisystemic disorder. It usually presents in toddler years with progressive ataxia and oculomotor apraxia, or less commonly, in the late-first or early-second decade of life with mixed movement disorders. Biallelic mutations in ataxia telangiectasia mutated gene (ATM) cause AT phenotype, a disease not well documented in Saudi Arabia, a highly consanguineous society. Read More

Ann Hum Genet 2022 03 24;86(2):63-70. Epub 2021 Sep 24.

School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P. R. China.

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 (HBB: c.-100G>A). Read More

Ann Hum Genet 2022 01 15;86(1):24-33. Epub 2021 Sep 15.

University College London Research Department of Genetics Evolution and Environment, London, UK.

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 of the well-known lactase gene, LCT, we address the issue of imputation in the context of variants that have become frequent in a limited number of modern population groups only recently, due to selection. Read More

Ann Hum Genet 2022 01 26;86(1):14-23. Epub 2021 Aug 26.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

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 interaction between the presence of the genetic variant of rs696217-ghrelin and nutritional intake and other major determinants of obesity and lipid profile was examined in the MASHAD study population. Read More

Ann Hum Genet 2022 01 9;86(1):1-13. Epub 2021 Aug 9.

Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Chennai, India.

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. Read More

Ann Hum Genet 2021 11 3;85(6):235-244. Epub 2021 Aug 3.

Key Laboratory of Biomedical Engineering & Technology of Shandong High School, Qilu Medical University, Zibo, P. R. China.

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 the result of a DE analysis. Read More