Articles

Toward a clinical diagnostic pipeline for SPINK1 intronic variants

The clinical significance of SPINK1 intronic variants in chronic pancreatitis has been previously assessed by various approaches including a cell culture-based full-length gene assay. A close correlation between ...

Authors: Xin-Ying Tang, Jin-Huan Lin, Wen-Bin Zou, Emmanuelle Masson, Arnaud Boulling, Shun-Jiang Deng, David N. Cooper, Zhuan Liao, Claude Férec, Zhao-Shen Li and Jian-Min Chen

The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau

The ability to digest dietary lactose is associated with lactase persistence (LP) in the intestinal lumen in human. The genetic basis of LP has been investigated in many populations in the world. Iran has a lo...

Authors: Hadi Charati, Min-Sheng Peng, Wei Chen, Xing-Yan Yang, Roghayeh Jabbari Ori, Mohsen Aghajanpour-Mir, Ali Esmailizadeh and Ya-Ping Zhang

A genome-wide association study of mitochondrial DNA copy number in two population-based cohorts

Mitochondrial DNA copy number (mtDNA CN) exhibits interindividual and intercellular variation, but few genome-wide association studies (GWAS) of directly assayed mtDNA CN exist.

Authors: Anna L. Guyatt, Rebecca R. Brennan, Kimberley Burrows, Philip A. I. Guthrie, Raimondo Ascione, Susan M. Ring, Tom R. Gaunt, Angela Pyle, Heather J. Cordell, Debbie A. Lawlor, Patrick F. Chinnery, Gavin Hudson and Santiago Rodriguez

The association of functional polymorphisms in genes expressed in endothelial cells and smooth muscle cells with the myocardial infarction

The association of platelet endothelial cell adhesion molecule 1 (PECAM1), hypoxia-inducible factor 1 subunit alpha (HIF1A), and KIAA1462 in myocardial infarction (MI) was investigated. The study included 401 ...

Authors: Yilan Li, Shipeng Wang, Dandan Zhang, Xueming Xu, Bo Yu and Yao Zhang

Germline TP53 and MSH6 mutations implicated in sporadic triple-negative breast cancer (TNBC): a preliminary study

Germline BRCA1/2 prevalence is relatively low in sporadic triple-negative breast cancer (TNBC). We hypothesized that non-BRCA genes may also have significant germline contribution to Chinese sporadic TNBC, and...

Authors: Dandan Yi, Lei Xu, Jiaqi Luo, Xiaobin You, Tao Huang, Yi Zi, Xiaoting Li, Ru Wang, Zaixuan Zhong, Xiaoqiao Tang, Ang Li, Yujian Shi, Jianmei Rao, Yifen Zhang and Jianfeng Sang

Population and breast cancer patients’ analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in c...

Authors: J. C. Fernández-Lopez, S. Romero-Córdoba, R. Rebollar-Vega, L. A. Alfaro-Ruiz, S. Jiménez-Morales, F. Beltrán-Anaya, R. Arellano-Llamas, A. Cedro-Tanda, M. Rios-Romero, M. Ramirez-Florencio, V. Bautista-Piña, C. Dominguez-Reyes, F. Villegas-Carlos, A. Tenorio-Torres and A. Hidalgo-Miranda

The X chromosome and sex-specific effects in infectious disease susceptibility

The X chromosome and X-linked variants have largely been ignored in genome-wide and candidate association studies of infectious diseases due to the complexity of statistical analysis of the X chromosome. This ...

Authors: Haiko Schurz, Muneeb Salie, Gerard Tromp, Eileen G. Hoal, Craig J. Kinnear and Marlo Möller

Preimplantation genetic diagnosis and screening (PGD/S) using a semiconductor sequencing platform

Recent advances in semiconductor sequencing platform (SSP) have provided new methods for preimplantation genetic diagnosis/screening (PGD/S). The present study aimed to evaluate the applicability and efficienc...

Authors: Li-Ya Wang, Xing-Qiang Rao, Yu-Qin Luo, Bei Liu, Chun-Fang Peng, Dan Chen, Kai Yan, Ye-Qing Qian, Yan-Mei Yang, Ying-Zhi Huang, Min Chen, Yi-Xi Sun, Hong-Ge Li, Ying-Hui Ye, Fan Jin, Hai-Liang Liu…

Identification of drug repurposing candidates based on a miRNA-mediated drug and pathway network for cardiac hypertrophy and acute myocardial infarction

Cardiac hypertrophy and acute myocardial infarction (AMI) are two common heart diseases worldwide. However, research is needed into the exact pathogenesis and effective treatment strategies for these diseases....

Authors: Jiantao Sun, Jiemei Yang, Jing Chi, Xue Ding and Nan Lv

Trans-activation-based risk assessment of BRCA1 BRCT variants with unknown clinical significance

Deleterious variants in the tumour suppressor BRCA1 are known to cause hereditary breast and ovarian cancer syndrome (HBOC). Missense variants in BRCA1 pose a challenge in clinical care, as their effect on protei...

Authors: Jonas Langerud, Elisabeth Jarhelle, Marijke Van Ghelue, Sarah Louise Ariansen and Nina Iversen

Perceptions of students in health and molecular life sciences regarding pharmacogenomics and personalized medicine

Increasing evidence is demonstrating that a patient’s unique genetic profile can be used to detect the disease’s onset, prevent its progression, and optimize its treatment. This led to the increased global eff...

Authors: Lejla Mahmutovic, Betul Akcesme, Camil Durakovic, Faruk Berat Akcesme, Aida Maric, Muhamed Adilovic, Nour Hamad, Matthias Wjst, Oliver Feeney and Sabina Semiz

Bayesian variable selection for parametric survival model with applications to cancer omics data

Modeling thousands of markers simultaneously has been of great interest in testing association between genetic biomarkers and disease or disease-related quantitative traits. Recently, an expectation-maximizati...

Authors: Weiwei Duan, Ruyang Zhang, Yang Zhao, Sipeng Shen, Yongyue Wei, Feng Chen and David C. Christiani

Multiple genotype–phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population

Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these v...

Authors: Sanghoon Moon, Young Lee, Sungho Won and Juyoung Lee

Link between short tandem repeats and translation initiation site selection

Despite their vast biological implication, the relevance of short tandem repeats (STRs)/microsatellites to the protein-coding gene translation initiation sites (TISs) remains largely unknown.

Authors: Masoud Arabfard, Kaveh Kavousi, Ahmad Delbari and Mina Ohadi

Identification of gross deletions in FBN1 gene by MLPA

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. Approximately 90% of classic MFS patients have a FBN1 mutation that can be identified by single-gene...

Authors: Hang Yang, Yanyun Ma, Mingyao Luo, Kun Zhao, Yinhui Zhang, Guoyan Zhu, Xiaogang Sun, Fanyan Luo, Lin Wang, Chang Shu and Zhou Zhou

Impact of ZBTB7A hypomethylation and expression patterns on treatment response to hydroxyurea

We aimed to clarify the emerging epigenetic landscape in a group of genes classified as “modifier genes” of the β-type globin genes (HBB cluster), known to operate in trans to accomplish the two natural developme...

Authors: Vasiliki Chondrou, Eleana F. Stavrou, Georgios Markopoulos, Alexandra Kouraklis-Symeonidis, Vasilios Fotopoulos, Argiris Symeonidis, Efthymia Vlachaki, Panagiota Chalkia, George P. Patrinos, Adamantia Papachatzopoulou and Argyro Sgourou

Identification of TBX2 and TBX3 variants in patients with conotruncal heart defects by target sequencing

Conotruncal heart defects (CTDs) are heterogeneous congenital heart malformations that result from outflow tract dysplasia; however, the genetic determinants underlying CTDs remain unclear. Increasing evidence...

Authors: Huilin Xie, Erge Zhang, Nanchao Hong, Qihua Fu, Fen Li, Sun Chen, Yu Yu and Kun Sun

Architecture of polymorphisms in the human genome reveals functionally important and positively selected variants in immune response and drug transporter genes

Genetic polymorphisms can contribute to phenotypic differences amongst individuals, including disease risk and drug response. Characterization of genetic polymorphisms that modulate gene expression and/or prot...

Authors: Yu Jin, Jingbo Wang, Maulana Bachtiar, Samuel S. Chong and Caroline G. L. Lee

Secondary findings in 421 whole exome-sequenced Chinese children

Variants with known or possible pathogenicity located in genes that are unrelated to primary disease conditions are defined as secondary findings. Secondary findings are not the primary targets of whole exome ...

Authors: Wen Chen, Wenke Li, Yi Ma, Yujing Zhang, Bianmei Han, Xuewen Liu, Kun Zhao, Meixian Zhang, Jie Mi, Yuanyuan Fu and Zhou Zhou

Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes

Studying epigenetics is expected to provide precious information on how environmental factors contribute to type 2 diabetes mellitus (T2DM) at the genomic level. With the progress of the whole-genome resequenc...

Authors: Chandrakumar Sathishkumar, Paramasivam Prabu, Viswanathan Mohan and Muthuswamy Balasubramanyam

Forward and reverse mutations in stages of cancer development

Massive occurrences of interstitial loss of heterozygosity (LOH) likely resulting from gene conversions were found by us in different cancers as a type of single-nucleotide variations (SNVs), comparable in abu...

Authors: Taobo Hu, Yogesh Kumar, Iram Shazia, Shen-Jia Duan, Yi Li, Lei Chen, Jin-Fei Chen, Rong Yin, Ava Kwong, Gilberto Ka-Kit Leung, Wai-Kin Mat, Zhenggang Wu, Xi Long, Cheuk-Hin Chan, Si Chen, Peggy Lee…

BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population

Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presen...

Authors: Florencia C. Cardoso, Susana Goncalves, Pablo G. Mele, Natalia C. Liria, Leonardo Sganga, Ignacio Diaz Perez, Ernesto J. Podesta and Angela R. Solano

The impact of genome-wide association studies on biomedical research publications

The past decade has seen major investment in genome-wide association studies (GWAS). Among the many goals of GWAS, a major one is to identify and motivate research on novel genes involved in complex human dise...

Authors: Travis J. Struck, Brian K. Mannakee and Ryan N. Gutenkunst

Associations of high-altitude polycythemia with polymorphisms in PIK3CD and COL4A3 in Tibetan populations

High-altitude polycythemia (HAPC) is a chronic high-altitude disease that can lead to an increase in the production of red blood cells in the people who live in the plateau, a hypoxia environment, for a long t...

Authors: Xiaowei Fan, Lifeng Ma, Zhiying Zhang, Yi Li, Meng Hao, Zhipeng Zhao, Yiduo Zhao, Fang Liu, Lijun Liu, Xingguang Luo, Peng Cai, Yansong Li and Longli Kang

A new bioinformatics tool to help assess the significance of BRCA1 variants

Germline pathogenic variants in the breast cancer type 1 susceptibility gene BRCA1 are associated with a 60% lifetime risk for breast and ovarian cancer. This overall risk estimate is for all BRCA1 variants; obvi...

Authors: Isabelle Cusin, Daniel Teixeira, Monique Zahn-Zabal, Valentine Rech de Laval, Anne Gleizes, Valeria Viassolo, Pierre O. Chappuis, Pierre Hutter, Amos Bairoch and Pascale Gaudet

A novel LRAT mutation affecting splicing in a family with early onset retinitis pigmentosa

Retinitis pigmentosa is an important cause of severe visual dysfunction. This study reports a novel splicing mutation in the lecithin retinol acyltransferase (LRAT) gene associated with early onset retinitis pigm...

Authors: Yabin Chen, Li Huang, Xiaodong Jiao, Sheikh Riazuddin, S. Amer Riazuddin and J. Fielding Hetmancik

Whole-exome sequencing identifies novel pathogenic mutations and putative phenotype-influencing variants in Polish limb-girdle muscular dystrophy patients

Limb girdle muscular dystrophies (LGMD) are a group of heterogeneous hereditary myopathies with similar clinical symptoms. Disease onset and progression are highly variable, with an elusive genetic background,...

Authors: Jakub Piotr Fichna, Anna Macias, Marcin Piechota, Michał Korostyński, Anna Potulska-Chromik, Maria Jolanta Redowicz and Cezary Zekanowski

Abundance of clinical variants in exons included in multiple transcripts

Previous studies showed that the magnitude of selection pressure in constitutive exons is higher than that in alternatively spliced exons. The intensity of selection was also shown to be depended on the inclus...

Authors: Sankar Subramanian

Caution needs to be taken when assigning transcription start sites to ends of protein-coding genes: a rebuttal

Naturally occurring stress-induced transcriptional readthrough is a recently discovered phenomenon, in which stress conditions lead to dramatic induction of long transcripts as a result of transcription termin...

Authors: Niv Sabath, Anna Vilborg, Joan A. Steitz and Reut Shalgi

The tale of histone modifications and its role in multiple sclerosis

Epigenetics defines the persistent modifications of gene expression in a manner that does not involve the corresponding alterations in DNA sequences. It includes modifications of DNA nucleotides, nucleosomal r...

Authors: Hui He, Zhiping Hu, Han Xiao, Fangfang Zhou and Binbin Yang

Computational analysis of mRNA expression profiling in the inner ear reveals candidate transcription factors associated with proliferation, differentiation, and deafness

Hearing loss is a major cause of disability worldwide, impairing communication, health, and quality of life. Emerging methods of gene therapy aim to address this morbidity, which can be employed to fix a genet...

Authors: Kobi Perl, Ron Shamir and Karen B. Avraham

Oxidative stress-induced chromosome breaks within the ABL gene: a model for chromosome rearrangement in nasopharyngeal carcinoma

The mechanism underlying chromosome rearrangement in nasopharyngeal carcinoma (NPC) remains elusive. It is known that most of the aetiological factors of NPC trigger oxidative stress. Oxidative stress is a pot...

Authors: Sang-Nee Tan, Sai-Peng Sim and Alan Soo-Beng Khoo

Associations between hypertension and the peroxisome proliferator-activated receptor-δ (PPARD) gene rs7770619 C>T polymorphism in a Korean population

Oxidative stress is associated with the increased risk of hypertension (HTN). This cross-sectional study is aimed to identify the association between the peroxisome proliferator-activated receptor-δ (PPARD) polym...

Authors: Minjoo Kim, Minkyung Kim, Hye Jin Yoo, Jayoung Shon and Jong Ho Lee

Integrating rare genetic variants into pharmacogenetic drug response predictions

Variability in genes implicated in drug pharmacokinetics or drug response can modulate treatment efficacy or predispose to adverse drug reactions. Besides common genetic polymorphisms, recent sequencing projec...

Authors: Magnus Ingelman-Sundberg, Souren Mkrtchian, Yitian Zhou and Volker M. Lauschke

Mutational analysis of epidermal and hyperproliferative type I keratins in mild and moderate psoriasis vulgaris patients: a possible role in the pathogenesis of psoriasis along with disease severity

Mutations in keratin proteins have been vastly associated with a wide array of genodermatoses; however, mutations of keratins in psoriasis have not been fully investigated. The main aim of the current research...

Authors: Tamilselvi Elango, Jingying Sun, Caihong Zhu, Fusheng Zhou, Yaohua Zhang, Liangdan Sun, Sen Yang and Xuejun Zhang

Nonparametric approaches for population structure analysis

The analysis of population structure has many applications in medical and population genetic research. Such analysis is used to provide clear insight into the underlying genetic population substructure and is ...

Authors: Luluah Alhusain and Alaaeldin M. Hafez

Better governance, better access: practising responsible data sharing in the METADAC governance infrastructure

Genomic and biosocial research data about individuals is rapidly proliferating, bringing the potential for novel opportunities for data integration and use. The scale, pace and novelty of these applications ra...

Authors: Madeleine J. Murtagh, Mwenza T. Blell, Olly W. Butters, Lorraine Cowley, Edward S. Dove, Alissa Goodman, Rebecca L. Griggs, Alison Hall, Nina Hallowell, Meena Kumari, Massimo Mangino, Barbara Maughan, Melinda C. Mills, Joel T. Minion, Tom Murphy, Gillian Prior…

Evaluation of a bone morphogenetic protein 6 variant as a cause of iron loading

Atypical iron overload without variation in the five clinically associated hereditary hemochromatosis genes is now recognized; however, their etiology remains unknown. Since the identification of iron overload...

Authors: Cameron J. McDonald, Gautam Rishi, Eriza S. Secondes, Lesa Ostini, Daniel F. Wallace, Darrell H. G. Crawford, Hanlon Sia, Paul Clark and V. Nathan Subramaniam

Tensions in ethics and policy created by National Precision Medicine Programs

Precision medicine promises to use genomics and other data-intensive approaches to improve diagnosis and develop new treatments for major diseases, but also raises a range of ethical and governance challenges....

Authors: Jusaku Minari, Kyle B. Brothers and Michael Morrison

Public attitudes in Japan toward participation in whole genome sequencing studies

Recent innovations in gene analysis technology have allowed for rapid and inexpensive sequencing of entire genomes. Thus, both conducting a study using whole genome sequencing (WGS) in a large population and t...

Authors: Taketoshi Okita, Noriko Ohashi, Daijiro Kabata, Ayumi Shintani and Kazuto Kato

Correlation of gene expression and associated mutation profiles of APOBEC3A, APOBEC3B, REV1, UNG, and FHIT with chemosensitivity of cancer cell lines to drug treatment

The APOBEC gene family of cytidine deaminases plays important roles in DNA repair and mRNA editing. In many cancers, APOBEC3B increases the mutation load, generating clusters of closely spaced, single-strand-spec...

Authors: Suleyman Vural, Richard Simon and Julia Krushkal

The development of large-scale de-identified biomedical databases in the age of genomics—principles and challenges

Contemporary biomedical databases include a wide range of information types from various observational and instrumental sources. Among the most important features that unite biomedical databases across the fie...

Authors: Fida K. Dankar, Andrey Ptitsyn and Samar K. Dankar

Molecular characterization of exonic rearrangements and frame shifts in the dystrophin gene in Duchenne muscular dystrophy patients in a Saudi community

In individuals with Duchenne muscular dystrophy (DMD), exon skipping treatment to restore a wild-type phenotype or correct the frame shift of the mRNA transcript of the dystrophin (DMD) gene are mutation-specific...

Authors: Nasser A. Elhawary, Essam H. Jiffri, Samira Jambi, Ahmad H. Mufti, Anas Dannoun, Hassan Kordi, Asim Khogeer, Osama H. Jiffri, Abdelrahman N. Elhawary and Mohammed T. Tayeb

Genome-scale portrait and evolutionary significance of human-specific core promoter tri- and tetranucleotide short tandem repeats

While there is an ongoing trend to identify single nucleotide substitutions (SNSs) that are linked to inter/intra-species differences and disease phenotypes, short tandem repeats (STRs)/microsatellites may be ...

Authors: N. Nazaripanah, F. Adelirad, A. Delbari, R. Sahaf, T. Abbasi-Asl and M. Ohadi

Large-scale discovery of previously undetected microRNAs specific to human liver

MicroRNAs (miRNAs) are crucial regulators of gene expression in normal development and cellular homeostasis. While miRNA repositories contain thousands of unique sequences, they primarily contain molecules tha...

Authors: Brenda C. Minatel, Victor D. Martinez, Kevin W. Ng, Adam P. Sage, Tomas Tokar, Erin A. Marshall, Christine Anderson, Katey S. S. Enfield, Greg L. Stewart, Patricia P. Reis, Igor Jurisica and Wan L. Lam

Transcription start sites at the end of protein-coding genes

Previous studies demonstrated that massive induction of transcriptional readthrough generates downstream of gene-containing transcripts (DoGs) in cells under stress condition. Here, we analyzed TSS-seq (transc...

Authors: Ming-Yu Huang and Ji-Long Liu

2-deoxy-2-[18]fluoro-D-glucose PET/CT (18FDG PET/CT) may not be a viable biomarker in Pompe disease

Pompe disease (PD) is an autosomal recessive, lysosomal storage disease due to a mutation of the acid α-glucosidase (GAA) gene. In adult patients, PD is characterized by slowly progressive limb-girdle and trunk m...

Authors: U. Plöckinger, V. Prasad, A. Ziagaki, N. Tiling and A. Poellinger

Abstracts from the Human Genome Meeting 2018

Authors:

Including all voices in international data-sharing governance

Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will b...

Authors: Jane Kaye, Sharon F. Terry, Eric Juengst, Sarah Coy, Jennifer R. Harris, Don Chalmers, Edward S. Dove, Isabelle Budin-Ljøsne, Clement Adebamowo, Emilomo Ogbe, Louise Bezuidenhout, Michael Morrison, Joel T. Minion, Madeleine J. Murtagh, Jusaku Minari, Harriet Teare…

Attitudes of stakeholders in psychiatry towards the inclusion of children in genomic research

Genomic sequencing of children in research raises complex ethical issues. This study aims to gain more knowledge on the attitudes towards the inclusion of children as research subjects in genomic research and ...

Authors: Anna Sundby, Merete Watt Boolsen, Kristoffer Sølvsten Burgdorf, Henrik Ullum, Thomas Folkmann Hansen and Ole Mors