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A novel c.3636-4 A>G mutation in the CCDC88C plays a causative role in familial spinocerebellar ataxia. Hum. Hered. (IF 1.8) Pub Date : 2023-10-27 Senmao Chai,Deyang Liu,Yajing Liu,Ming Sang
INTRODUCTION Spinocerebellar ataxia (SCA) is an autosomal dominant genetic disease characterized by cerebellar neurological deficits. Specifically, its primary clinical manifestation is ataxia accompanied by peripheral nerve damage. A total of 48 causative genes of SCA have been identified. This study aimed to identify causative genes of autosomal dominant SCA in a four-generation Chinese kindred comprised
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The diagnostic value of miR-124a expression in peripheral blood and synovial fluid of patients with rheumatoid arthritis. Hum. Hered. (IF 1.8) Pub Date : 2023-06-14 Tianhao Wu,Yanlong Zhang,Aqin Peng,Xirui Wu
INTRODUCTION Rheumatoid arthritis (RA), a chronic autoimmune disorder, is currently a severe health threat. Previous studies have documented the altered expression of various miRNAs in RA patients. This study determined the expression of miR-124a in RA patients and estimated its diagnostic value for RA. METHODS Total 80 RA patients were enrolled as the study subjects and 36 patients with osteoarthritis
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A novel PMVK variant associated with familial porokeratosis. Hum. Hered. (IF 1.8) Pub Date : 2023-06-14 Wenjing Zhang,Xinmiao Nie,Lei Shi,Fengmin Shao,Lihua Cao
Introduction Porokeratosis is a rare chronic progressive hypokeratotic skin disease, possibly related to the mevalonate pathway. Variations in four enzymes, including phosphomevalonate kinase (PMVK) may alter this pathway, ultimately leading to porokeratosis. Methods In this study, Sanger sequencing was used to identify the gene variant causative of porokeratosis; its population frequency was investigated
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Methods and software to analyze gene-environment interactions under a case-mother - control-mother design with partially missing child genotype Hum. Hered. (IF 1.8) Pub Date : 2023-04-26 Alexandre Bureau, Yuang Tian, Patrick Levallois, Yves Giguère, Jinbo Chen, Hong Zhang
Introduction: The case-mother - control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early-life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties
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A common variant of ARRB2 promoter region Associated with the Prognosis of Heart Failure Hum. Hered. (IF 1.8) Pub Date : 2023-04-26 Hongqiang Ren, Yijun liu, Zhen Tan, Guiquan Luo, Mei Zhang, Shuang Li, Tingwei Tang, Zhao Li
Introduction The role of ARRB2 in cardiovascular disease has recently gained increasing attention. However, the association between ARRB2 polymorphisms and heart failure (HF) has not yet been investigated. Methods A total of 2386 hospitalized patients with chronic heart failure were enrolled as the first cohort and followed up for a mean period of 20.2 months. Meanwhile, ethnically and geographically
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Polymorphisms of placental iodothyronine deiodinase genes in a rural area of Northern China with high prevalence of neural tube defects Hum. Hered. (IF 1.8) Pub Date : 2023-03-21 Fang Wang, Yan-Hong Gu, Jin Guo, YiHua Bao, ZhiYong Qiu, Ping Zheng, Masaru Ushijima, Masaaki Matsuura, Ting Zhang
Introduction: We have reported that high total homocysteine (tHCY), and the coexistence of inadequate thyroid hormones in maternal serum increase the risk of fetal neural tube defects (NTDs). Placental iodothyronine deiodinases (DIOs: DIO1, DIO2, and DIO3) play a role in regulate the conversions between different forms of maternal thyroid hormones. This study hypothesized that single nucleotide polymorphisms
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Identification of a hypoxia-related signature as candidate detector for schizophrenia based on genome-wide gene expression Hum. Hered. (IF 1.8) Pub Date : 2023-03-13 Zhitao Li, Xinyu Sun, Jia He, Dongyan Kong, Jinyi Wang, Lili Wang
Introduction: Schizophrenia (SCZ), a severe neuropsychiatric disorder with high genetic susceptibility, has high rates of misdiagnosis due to the unavoidably subjective factors and heterogeneous clinical presentations. Hypoxia has been identified as an importantly risk factor that participates in the development of SCZ. Therefore, development of a hypoxia-related biomarker for SCZ diagnosis is promising
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A comprehensive study of mutations in PAH, QDPR, PTS, and PCD genes in Iranian patients with Hyperphenylalaninemia; A systematic review Hum. Hered. (IF 1.8) Pub Date : 2023-01-16 Mahmoud Ghanei, Seyedeh Helia Sadat Fatemi, Tayebeh Hamzehlouei
Background: Hyperphenylalaninemia (HPA) is an autosomal recessive disorder that results from a deficiency in the phenylalanine hydroxylase enzyme (PAH) or from a flaw in the genes that are responsible for the biosynthesis or regeneration of the cofactor tetrahydrobiopterin (BH4), including GCH1, SR, QDPR, PTS, and PCD. Identification of disease-causing variants in these genes can help physicians and
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Reduction of missed diagnosis of G6PD deficiency in heterozygous females by G6PD/6PGD ratio assay combined with ARMS-PCR Hum. Hered. (IF 1.8) Pub Date : 2022-10-31 Shiguo Chen, Jian Gao, Qunyan Wu, Xi Li, Sheng Lin, Jindi Su, Kaifeng Zheng, Zhaopeng Guo, Jilong Yao, Shan Duan
Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. The G6PD/6PGD ratio assay was routinely used for G6PD deficiency screening in China, but there is an apparent defect of missed diagnosis in heterozygous females. The study aims to explore the means to improve its accuracy. Methods: A total of 4161 Chinese females
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Reduction of missed diagnosis of G6PD deficiency in heterozygous females by G6PD/6PGD ratio assay combined with ARMS-PCR Hum. Hered. (IF 1.8) Pub Date : 2022-10-31
Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. The G6PD/6PGD ratio assay was routinely used for G6PD deficiency screening in China, but there is an apparent defect of missed diagnosis in heterozygous females. The study aims to explore the means to improve its accuracy. Methods: A total of 4161 Chinese females
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The prevalence of JAK2 exon12 mutations in Vietnamese patients with JAK2 V617F-negative polycythemia vera: frequent or rare? Hum. Hered. (IF 1.8) Pub Date : 2022-08-03 Ngoc T. Nguyen, Linh T. Nguyen, Xuan T. Nguyen
Purpose Polycythemia vera is a hematological malignancy characterized by the overproduction of red blood cells in the bone marrow. Pathogenesis of Polycythemia vera was thought to be caused by genetic mutations of the Janus kinase 2 (JAK2) gene, especially the JAK2 V617F and exon 12 mutations since those mutations were found frequently in the patients. The prevalence of JAK2 exon 12 mutations among
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The Prevalence of JAK2 Exon 12 Mutations in Vietnamese Patients with JAK2 V617F-Negative Polycythemia Vera: Frequent or Rare? Hum. Hered. (IF 1.8) Pub Date : 2022-08-03
Purpose: Polycythemia vera is a hematological malignancy characterized by the overproduction of red blood cells in the bone marrow. Pathogenesis of polycythemia vera was thought to be caused by genetic mutations of the Janus kinase 2 (JAK2) gene, especially the JAK2 V617F and exon 12 mutations, since those mutations were found frequently in the patients. The prevalence of JAK2 exon 12 mutations among
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Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-eclampsia Hum. Hered. (IF 1.8) Pub Date : 2022-07-18 Baohua Zhou, Xuelian Chu, Caijuan Zhang, Xiufeng Liang
Objectives: Impairment of mitochondrial function caused by pathogenic mitochondrial DNA (mtDNA) mutations has been found to be associated with pre-eclampsia (PE). However, the underlying mechanism of PE remains poorly undetermined. The aim of this study is to evaluate the relationship between mitochondrial tRNAs (mt-tRNAs) variants and PE. Material and Methods: The mt-tRNAs variants in a cohort of
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Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-Eclampsia Hum. Hered. (IF 1.8) Pub Date : 2022-07-18
Introduction: Impairment of mitochondrial function caused by pathogenic mitochondrial DNA (mtDNA) mutations has been found to be associated with pre-eclampsia (PE). However, the underlying mechanism of PE remains poorly undetermined. The aim of this study is to evaluate the relationship between mitochondrial tRNA (mt-tRNA) variants and PE. Methods: The mt-tRNA variants in a cohort of 100 pregnant women
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Penalized Logistic Regression Analysis for Genetic Association Studies of Binary Phenotypes Hum. Hered. (IF 1.8) Pub Date : 2022-06-29 Ying Yu, Siyuan Chen, Samantha Jean Jones, Rawnak Hoque, Olga Vishnyakova, Angela Brooks-Wilson, Brad McNeney
Introduction: Increasingly, logistic regression methods for genetic association studies of binary phenotypes must be able to accommodate data sparsity, which arises from unbalanced case-control ratios and/or rare genetic variants. Sparseness leads to maximum likelihood estimators (MLEs) of log-OR parameters that are biased away from their null value of zero and tests with inflated type 1 errors. Different
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Penalized Logistic Regression Analysis for Genetic Association Studies of Binary Phenotypes Hum. Hered. (IF 1.8) Pub Date : 2022-06-29
Introduction: Increasingly, logistic regression methods for genetic association studies of binary phenotypes must be able to accommodate data sparsity, which arises from unbalanced case-control ratios and/or rare genetic variants. Sparseness leads to maximum likelihood estimators (MLEs) of log-OR parameters that are biased away from their null value of zero and tests with inflated type I errors. Different
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Common variants in Neuraminidases genes contribute to predisposition to and progression of chronic heart failure Hum. Hered. (IF 1.8) Pub Date : 2022-06-28 Shiyang Li, Yuehong Wang, Xiaobing Zeng, Yanyu Zhang, Shihai Wang, Yuyong Liu, Dawen Xu, Jianjun Lan, Dong Hu
Introduction The role of neuraminidases in cardiovascular disease has recently gained increasing attention. However, the association between neuraminidase gene polymorphisms and heart failure (HF) has not yet been investigated. Methods and Results Genotyping of nine single nucleotide polymorphisms (SNPs) in the NEU2/NEU3/NEU4 genes was performed in 610 HF patients and 600 healthy controls from the
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Common Variants in Neuraminidase Genes Contribute to Predisposition to and Progression of Chronic Heart Failure Hum. Hered. (IF 1.8) Pub Date : 2022-06-28
Introduction: The role of neuraminidases in cardiovascular disease has recently gained increasing attention. However, the association between neuraminidase gene polymorphisms and heart failure (HF) has not yet been investigated. Methods and Results: Genotyping of nine single-nucleotide polymorphisms (SNPs) in the NEU2/NEU3/NEU4 genes was performed in 610 HF patients and 600 healthy controls from the
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Identification of a novel mutation in patients with type A insulin resistance syndrome Hum. Hered. (IF 1.8) Pub Date : 2022-06-03 Liling Zhao, Hongmei Dai, Qin Zhang, Wenmu Hu, Ping Jin
Introduction: Type A insulin resistance syndrome is a rare type of congenital insulin resistance often caused by heterozygous mutations in the insulin receptor gene (INSR). The aim of this study is to explore the clinical and genetic characteristics of three patients with type A insulin resistance syndrome from two Chinese families. Methods: The peripheral blood samples were collected from each family
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Identification of a Novel Mutation in Patients with Type A Insulin Resistance Syndrome Hum. Hered. (IF 1.8) Pub Date : 2022-06-03
Introduction: Type A insulin resistance syndrome is a rare type of congenital insulin resistance often caused by heterozygous mutations in the insulin receptor gene (INSR). The aim of this study was to explore the clinical and genetic characteristics of three patients with type A insulin resistance syndrome from two Chinese families. Methods: The peripheral blood samples were collected from each family
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50th European Mathematical Genetics Meeting (EMGM) 2022 Hum. Hered. (IF 1.8) Pub Date : 2022-04-20
Hum Hered 2022;Vol.:1–42
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50th European Mathematical Genetics Meeting (EMGM) 2022 Hum. Hered. (IF 1.8) Pub Date : 2022-04-20
Hum Hered 2022;Vol.:1–42
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The mitochondrial tRNAAsp T7561C, tRNAHis C12153T and A12172G mutations may be associated with essential hypertension in a Han Chinese pedigree Hum. Hered. (IF 1.8) Pub Date : 2022-03-28 Haiying Fu, Jinming Sun, Xiaoyan Xu
Objectives: Mutations in mitochondrial tRNA (mt-tRNA) are the important causes for maternally inherited hypertension, however, the pathophysiology of mt-tRNA mutations in clinical expression of hypertension remains poorly understood. Material and Methods: In this study, we report the molecular features of a Han Chinese pedigree with maternally transmitted essential hypertension. The entire mitochondrial
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The Mitochondrial tRNAAsp T7561C, tRNAHis C12153T, and A12172G Mutations May Be Associated with Essential Hypertension in a Han Chinese Pedigree Hum. Hered. (IF 1.8) Pub Date : 2022-03-28
Objectives: Mutations in mitochondrial tRNA (mt-tRNA) are the important causes for maternally inherited hypertension; however, the pathophysiology of mt-tRNA mutations in clinical expression of hypertension remains poorly understood. Material and Methods: In this study, we report the molecular features of a Han Chinese pedigree with maternally transmitted essential hypertension. The entire mitochondrial
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Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts Hum. Hered. (IF 1.8) Pub Date : 2022-02-16 Rasha N. Alotaibi, Brian J. Howe, Lina M. Moreno Uribe, Carla Sanchez, Frederic W.B. Deleyiannis, Carmencita Padilla, Fernando A. Poletta, Ieda M. Orioli, Carmen J. Buxó, George L. Wehby, Alexandre R. Vieira, Jeffrey Murray, Consuelo Valencia-Ramírez, Claudia P. Restrepo Muñeton, Ross E. Long, John R. Shaffer, Steven E. Reis, Seth M. Weinberg, Katherine Neiswanger, Daniel W. McNeil, Mary L. Marazita
Enamel hypoplasia causes reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. A genome-wide association of enamel hypoplasia was performed in multiple cohorts
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Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts Hum. Hered. (IF 1.8) Pub Date : 2022-02-16
Introduction: Enamel hypoplasia causes a reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. Methods: A genome-wide association of enamel hypoplasia was performed
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Identification of CHEK2 germline mutations in BRCA1/2 and PALB2 negative breast and ovarian cancer patients Hum. Hered. (IF 1.8) Pub Date : 2022-01-06 Fuat Aksoy, Havva Tezcan Unlu, Gulsah Cecener, Gamze Guney Eskiler, Unal Egeli, Berrin Tunca, Ecem Efendi Erdem, Kazım Senol, Mustafa Sehsuvar Gokgoz
Introduction: The CHEK2 gene is known to be an important signal transducer involved in DNA repair, apoptosis, or cell cycle arrest in response to DNA damage. The mutations in this gene have been associated with a wide range of cancers, both sporadic and hereditary. Germline CHEK2 mutations are linked to an increased risk of breast cancer. Therefore, the aim of this study was to identify the prevalence
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Screening for Mitochondrial tRNA Mutations in 318 Patients with Dilated Cardiomyopathy Hum. Hered. (IF 1.8) Pub Date : 2022-01-06 Yujuan Qi, Zhenhua Wu, Yaobang Bai, Yan Jiao, Peijun Li
Objectives: Dilated cardiomyopathy (DCM) is a complex cardiovascular disease with unknown etiology. Although nuclear genes play active roles in DCM, mitochondrial dysfunction was believed to be involved in the pathogenesis of DCM. The objective of this study is to analysis the association between mitochondrial tRNA (mt-tRNA) mutations and DCM. Material and Methods: We performed a mutational analysis
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Screening for Mitochondrial tRNA Mutations in 318 Patients with Dilated Cardiomyopathy Hum. Hered. (IF 1.8) Pub Date : 2022-01-06
Objectives: Dilated cardiomyopathy (DCM) is a complex cardiovascular disease with unknown etiology. Although nuclear genes play active roles in DCM, mitochondrial dysfunction was believed to be involved in the pathogenesis of DCM. The objective of this study was to analyze the association between mitochondrial tRNA (mt-tRNA) mutations and DCM. Materials and Methods: We performed a mutational analysis
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Family history of breast cancer is associated with elevated risk of prostate cancer: evidence for shared genetic risks Hum. Hered. (IF 1.8) Pub Date : 2021-11-30 Adrián Calvo Chozas, Behrang Mahjani, Lars Rönnegård
Introduction: Although breast and prostate cancers arise in different organs and are more frequent in the opposite sex, multiple studies have reported an association between their family history. Analysis of single nucleotide polymorphism data, based on distant relatives, has revealed a small positive genetic correlation between these cancers explained by common variants. The estimate of genetic correlation
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Association of PNPLA3 I148M with liver disease biomarkers in Latinos Hum. Hered. (IF 1.8) Pub Date : 2021-11-08 Jonathan D. Roe, Luis A. Garcia, Yann C. Klimentidis, Dawn K. Coletta
Introduction. Liver disease accounts for approximately 2 million deaths per year worldwide. The majority of liver diseases are due to complications of cirrhosis, viral hepatitis, and hepatocellular carcinoma. Increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may indicate liver disease. Moreover, there are additional noninvasive liver fibrosis indices that help
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Exome-Wide Pan-Cancer Analysis of Germline Variants in 8,719 Individuals Finds Little Evidence of Rare Variant Associations Hum. Hered. (IF 1.8) Pub Date : 2021-10-29 Zoe Guan, Ronglai Shen, Colin B. Begg
Background: Many cancer types show considerable heritability, and extensive research has been done to identify germline susceptibility variants. Linkage studies have discovered many rare high-risk variants, and genome-wide association studies (GWAS) have discovered many common low-risk variants. However, it is believed that a considerable proportion of the heritability of cancer remains unexplained
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Importance of Family History in the Era of Exome Analysis: A Report of a Family with Multiple Concurrent Genetic Diseases Hum. Hered. (IF 1.8) Pub Date : 2021-10-27 Karishma Mahtani, Diana Park, Jessica Abbott, Pavalan Panneer Selvam, Paldeep S. Atwal
Multiple familial diseases in a single patient often present with overlapping symptomatology that confers difficulty in delineating a clinical diagnosis. Pedigree analysis has been a long-standing practice in the field of medical genetics to discover familial diseases. In recent years, whole exome sequencing (WES) has proven to be a useful tool for aiding physicians in diagnosing and understanding
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Meta-Analysis of Joint Test of SNP and SNP-Environment Interaction with Heterogeneity Hum. Hered. (IF 1.8) Pub Date : 2021-10-26 Qinqin Jin, Gang Shi
Many complex diseases are caused by single nucleotide polymorphisms (SNPs), environmental factors, and the interaction between SNPs and environment. Joint tests of the SNP and SNP-environment interaction effects (JMA) and meta-regression (MR) are commonly used to evaluate these SNP-environment interactions. However, these two methods do not consider genetic heterogeneity. We previously presented a
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PhosSNPs-Regulated Gene Network and Pathway Significant for Rheumatoid Arthritis Hum. Hered. (IF 1.8) Pub Date : 2021-09-20 Pei He, Fei Jiang, Wei Guo, Yu-Fan Guo, Shu-Feng Lei, Fei-Yan Deng
Objectives: Peripheral blood mononuclear cells (PBMCs) are critical for immunity and participate in multiple human diseases, including rheumatoid arthritis (RA). PhosSNPs are nonsynonymous SNPs influencing protein phosphorylation, thus probably modulate cell signaling and gene expression. We aimed to identify phosSNPs-regulated gene network/pathway potentially significant for RA. Methods: We collected
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Putative Digenic GJB2/MYO7A Inheritance of Hearing Loss Detected in a Patient with 48,XXYY Klinefelter Syndrome Hum. Hered. (IF 1.8) Pub Date : 2021-06-30 Qin Zhang, Tiantian Qin, Wenmu Hu, Muhammad Usman Janjua, Ping Jin
Objectives: Nonsyndromic hearing loss (NSHL) is the most frequent type of hereditary hearing impairment. Here, we explored the underlying genetic cause of NSHL in a three-generation family using whole-exome sequencing. The proband had concomitant NSHL and rare 48,XXYY Klinefelter syndrome. Material and Methods: Genomic DNA was extracted from the peripheral blood of the proband and their family members
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Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in the Shenzhen Population Hum. Hered. (IF 1.8) Pub Date : 2021-06-16 Jian Gao, Sheng Lin, Shiguo Chen, Qunyan Wu, Kaifeng Zheng, Jindi Su, Zhaopeng Guo, Shan Duan
Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. This study aimed to characterize the G6PD gene variant distribution in Shenzhen of Guangdong province. Methods: A total of 33,562 individuals were selected at the hospital for retrospective analysis, of which 1,213 cases with enzymatic activity-confirmed G6PD deficiency
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Voltage-Gated Sodium Channel β1 Gene: An Overview Hum. Hered. (IF 1.8) Pub Date : 2021-05-26 Hisham Al-Ward, Chun-Yang Liu, Ning Liu, Fahmi Shaher, Murad Al-Nusaif, Jing Mao, Hui Xu
Background: Voltage-gated sodium channels are protein complexes composed of 2 subunits, namely, pore-forming α- and regulatory β-subunits. A β-subunit consists of 5 proteins encoded by 4 genes (i.e., SCN1B–SCN4B). Summary: β1-Subunits regulate sodium ion channel functions, including gating properties, subcellular localization, and kinetics. Key Message: Sodium channel β1- and its variant β1B-subunits
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49th European Mathematical Genetics Meeting (EMGM) 2021 Hum. Hered. (IF 1.8) Pub Date : 2021-04-20 Emmanuelle Génin
Hum Hered
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Methylenetetrahydrofolate Reductase Dimer Configuration as a Risk Factor for Maternal Meiosis I-Derived Trisomy 21 Hum. Hered. (IF 1.8) Pub Date : 2021-03-30 Jadranka Vraneković, Ivana Babić Božović, Iva Bilić Čače, Bojana Brajenović Milić
Background: Evidence suggests that the dimer configuration of methylenetetrahydrofolate reductase (MTHFR) enzyme might be destabilized by polymorphisms in monomers at the positions C677T and A1298C. It has been observed that these polymorphisms may lead to stable (CCAA, CCAC, CCCC) and unstable (CTAA, CTAC, TTAA) enzyme dimer configurations. Objective: The aim of this study was to evaluate the association
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Variants in ACE2 and TMPRSS2 Genes Are Not Major Determinants of COVID-19 Severity in UK Biobank Subjects Hum. Hered. (IF 1.8) Pub Date : 2021-03-22 David Curtis
It is plausible that variants in the ACE2 and TMPRSS2 genes might contribute to variation in COVID-19 severity and that these could explain why some people become very unwell whereas most do not. Exome sequence data was obtained for 49,953 UK Biobank subjects, of whom 82 had tested positive for SARS-CoV-2 and could be presumed to have severe disease. A weighted burden analysis was carried out using
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Combined Genotype Effects of TP53 and PAI-1 Polymorphisms in Breast Cancer Susceptibility: Multifactor Dimensionality Reduction and in silico Analysis Hum. Hered. (IF 1.8) Pub Date : 2021-03-18 Nasser Pouladi, Mojtaba Shavali, Sepehr Abdolahi
Introduction: Breast cancer is a heterogeneous and multifactorial disease. TP53 and PAI-1 as important tumor suppressor genes are involved in the development, invasion, and metastasis of many cancers. This study’s objective was to demonstrate the combined genotype effects of these 2 genes by investigating their single nucleotide polymorphisms. Methods: In this case-control study, 200 individuals with
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HLA Profile of Kami Population Refutes the Earlier Proposition of Exclusive Closer Genetic Affinity of All the Gorkhas to Mongoloids Hum. Hered. (IF 1.8) Pub Date : 2021-02-16 Bisu Singh, Dependra Chamlagai, Jiwan Gurung
Objective: Based on the HLA profile of Indian Gorkhas, Debnath and Chaudhuri (2006) proposed that Gorkhas are genetically closer to Mongoloids, and they may have originated from Mongolians or Tibetan stocks. However, the major limitation of the earlier study was that Gorkhas comprise 2 broad groups, i.e. Tibeto-Burmans and Indo-Aryans. Besides, Gorkhas have an assemblage of many sociocultural and linguistically
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Challenges of Adjusting Single-Nucleotide Polymorphism Effect Sizes for Linkage Disequilibrium Hum. Hered. (IF 1.8) Pub Date : 2021-02-12 Valentina Escott-Price, Karl Michael Schmidt
Background: Genome-wide association studies (GWAS) were successful in identifying SNPs showing association with disease, but their individual effect sizes are small and require large sample sizes to achieve statistical significance. Methods of post-GWAS analysis, including gene-based, gene-set and polygenic risk scores, combine the SNP effect sizes in an attempt to boost the power of the analyses.
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Identification of Influential Variants in Significant Aggregate Rare Variant Tests Hum. Hered. (IF 1.8) Pub Date : 2021-02-10 Rachel Z. Blumhagen, David A. Schwartz, Carl D. Langefeld, Tasha E. Fingerlin
Introduction: Studies that examine the role of rare variants in both simple and complex disease are increasingly common. Though the usual approach of testing rare variants in aggregate sets is more powerful than testing individual variants, it is of interest to identify the variants that are plausible drivers of the association. We present a novel method for prioritization of rare variants after a
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Asbestos-Induced Lung Cancer-Associated SNP rs13383928 Regulates PTH2R Expression in Lung Tissue Hum. Hered. (IF 1.8) Pub Date : 2021-02-05 Yuan-Qing Meng, Qiang Shi, Si-Jing Zhu, Guang-Huan He, Shi-Jiao Zhang, Chang Sun
Background: Lung cancer is one of the most common malignant tumors, and asbestos exposure was suggested to contribute to a proportion of lung cancer cases. Previous genome-wide gene-environment interaction analysis reported that rs13383928 was associated with asbestos-related lung cancer. However, the mechanism of this association was still unclear. Methods: In the present study, we retrieved the genotype
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Novel Mutation in AIFM1 Gene Associated with X-Linked Deafness in a Moroccan Family Hum. Hered. (IF 1.8) Pub Date : 2021-01-22 Soukaina Elrharchi, Zied Riahi, Sara Salime, Hicham Charoute, Lamiae Elkhattabi, Redouane Boulouiz, Mostafa Kabine, Crystel Bonnet, Christine Petit, Abdelhamid Barakat
Introduction: Auditory neuropathy is a hearing disorder where outer hair cell function within the cochlea is normal, but inner hair cell and/or the auditory nerve function is disrupted. It is a heterogeneous disorder, which can have either congenital or acquired causes. Methods: We found a disease-segregating mutation in the X-linked AIFM1 gene through whole-exome sequencing, encoding the apoptosis-inducing
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Multiple Linear Regression Allows Weighted Burden Analysis of Rare Coding Variants in an Ethnically Heterogeneous Population Hum. Hered. (IF 1.8) Pub Date : 2021-01-07 David Curtis
Weighted burden analysis has been used in exome-sequenced case-control studies to identify genes in which there is an excess of rare and/or functional variants associated with phenotype. Implementation in a ridge regression framework allows simultaneous analysis of all variants along with relevant covariates, such as population principal components. In order to apply the approach to a quantitative
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Novel IDS Variants Identified in Three Unrelated Pakistani Patients Affected with Mucopolysaccharidosis Type II (Hunter Syndrome) Hum. Hered. (IF 1.8) Pub Date : 2020-10-19 Bibi Zubaida, Hajira Batool, Huma Arshad Cheema, Nadia Waheed, Muhammad Naeem
Introduction: Mucopolysaccharidosis type II (MPS-II) or Hunter syndrome is a rare X-linked recessive disorder caused by genetic lesions in the IDS gene, encoding the iduronate-2-sulfatase (IDS) enzyme, disrupting the metabolism of certain sulfate components of the extracellular matrix. Thus, the undegraded components, also known as glycosaminoglycans, accumulate in multiple tissues resulting in multisystemic
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A Homozygous RAG1 Gene Mutation in a Case of Combined Immunodeficiency: Clinical, Molecular, and Computational Analysis Hum. Hered. (IF 1.8) Pub Date : 2020-10-19 Soukaina Essadssi, Ibtihal Benhsaien, Amina Bakhchane, Hicham Charoute, Houria Abdelghaffar, Ahmed Aziz Bousfiha, Abdelhamid Barakat
Background: The recombination-activating gene 1 and 2 (RAG1/RAG2) proteins are essential to initiate the V(D)J recombination process, the result is a diverse repertoire of antigen receptor genes and the establishment of the adaptive immunity. RAG1 mutations can lead to multiple forms of combined immunodeficiency. Methods: In this report, whole exome sequencing was performed in a Moroccan child suffering
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A Bayesian Hierarchical Framework for Pathway Analysis in Genome-Wide Association Studies. Hum. Hered. (IF 1.8) Pub Date : 2020-09-23 Lei Zhang,Charalampos Papachristou,Pankaj K Choudhary,Swati Biswas
Background: Pathway analysis allows joint consideration of multiple SNPs belonging to multiple genes, which in turn belong to a biologically defined pathway. This type of analysis is usually more powerful than single-SNP analyses for detecting joint effects of variants in a pathway. Methods: We develop a Bayesian hierarchical model by fully modeling the 3-level hierarchy, namely, SNP-gene-pathway that
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The Role of miR-210 in the Biological System: A Current Overview. Hum. Hered. (IF 1.8) Pub Date : 2020-09-09 Xu Hui,Hisham Al-Ward,Fahmi Shaher,Chun-Yang Liu,Ning Liu
Background: MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. Summary: miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance
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Power and Sample Size Calculations for Genetic Association Studies in the Presence of Genetic Model Misspecification. Hum. Hered. (IF 1.8) Pub Date : 2020-07-28 Camille M Moore,Sean A Jacobson,Tasha E Fingerlin
Introduction: When analyzing data from large-scale genetic association studies, such as targeted or genome-wide resequencing studies, it is common to assume a single genetic model, such as dominant or additive, for all tests of association between a given genetic variant and the phenotype. However, for many variants, the chosen model will result in poor model fit and may lack statistical power due
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Publisher's Note. Hum. Hered. (IF 1.8) Pub Date : 2020-06-19 P.-C. Sham, Françoise Clerget-Darpoux, Veronica Vieland, Neda Gharani, David B. Allison, Thomas Lehner, Rosalind Joyce Neuman, Derek Gordon, Marcella Devoto, Guido Barbujani, Michael Boehnke, Linda Brzustowicz, Hemant K. Tiwari, Michael Knapp, Cathryn Lewis, Rémi Kazma, Hervé Perdry, Mariza de Andrade, Y.Y. Teo, Frank Dudbridge, Katherine Montague, Emmanuelle Génin, Satz Mengensatzproduktion, Druckerei
Hum Hered
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Unbalanced Sample Size Introduces Spurious Correlations to Genome-Wide Heterozygosity Analyses. Hum. Hered. (IF 1.8) Pub Date : 2020-06-15 Li Liu,Richard J Caselli
Excess of heterozygosity (H) is a widely used measure of genetic diversity of a population. As high-throughput sequencing and genotyping data become readily available, it has been applied to investigating the associations of genome-wide genetic diversity with human diseases and traits. However, these studies often report contradictory results. In this paper, we present a meta-analysis of five whole-exome
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Test Gene-Environment Interactions for Multiple Traits in Sequencing Association Studies. Hum. Hered. (IF 1.8) Pub Date : 2020-05-16 Jianjun Zhang,Qiuying Sha,Han Hao,Shuanglin Zhang,Xiaoyi Raymond Gao,Xuexia Wang
Motivation: The risk of many complex diseases is determined by an interplay of genetic and environmental factors. The examination of gene-environment interactions (G×Es) for multiple traits can yield valuable insights about the etiology of the disease and increase power in detecting disease-associated genes. However, the methods for testing G×Es for multiple traits are very limited. Method: We developed
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48th European Mathematical Genetics Meeting (EMGM) 2020. Hum. Hered. (IF 1.8) Pub Date : 2020-04-08 Zoltan Kutalik
Hum Hered
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Frequency of BRCA1 and BRCA2 Mutations in Individuals with Breast and Ovarian Cancer in a Chinese Hakka Population Using Next-Generation Sequencing. Hum. Hered. (IF 1.8) Pub Date : 2020-02-26 Heming Wu,Qiuming Wang,Xuemin Guo,Qinghua Liu,Qunji Zhang,Qingyan Huang,Zhikang Yu
Background: It is necessary to investigate the frequency of BRCA1 and BRCA2 mutations in Hakka populations due to the variations in breast cancer epidemiology and genetics. Methods: 359 breast cancer patients and 66 ovarian cancer patients were included in this retrospective clinical study. Mutations of BRCA1 and BRCA2 were detected in blood samples by semiconductor sequencing. Results: The sensitivity
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Heritability and Sex-Specific Genetic Effects of Self-Reported Physical Activity in a Brazilian Highly Admixed Population. Hum. Hered. (IF 1.8) Pub Date : 2020-02-21 Jean Michel Rocha Sampaio Leite,Júlia Maria Pavan Soler,Andréa Roseli Vançan Russo Horimoto,Rafael O Alvim,Alexandre C Pereira
Introduction: The engagement in sports or habitual physical activity (PA) has shown an extensive protective role against multiple diseases such as cancer, obesity, and many others. Additionally, PA has also a significant impact on life quality, since it aids with managing stress, preserving cognitive function and memory, and preventing fractures in the elderly. Objective: Considering there has been