Articles

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

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

A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features

Intellectual disability (ID) is a common condition with a population prevalence frequency of 1–3% and an enrichment for males, driven in part by the contribution of mutant alleles on the X-chromosome. Among th...

Authors: Georgios Kellaris, Kamal Khan, Shahid M. Baig, I-Chun Tsai, Francisca Millan Zamora, Paul Ruggieri, Marvin R. Natowicz and Nicholas Katsanis

Yale School of Public Health Symposium on tissue imaging mass spectrometry: illuminating phenotypic heterogeneity and drug disposition at the molecular level

Authors: Georgia Charkoftaki, Nicholas J. W. Rattray, Per E. Andrén, Richard M. Caprioli, Steve Castellino, Mark W. Duncan, Richard J. A. Goodwin, Kevin L. Schey, Sheerin K. Shahidi-Latham, Kirill A. Veselkov, Caroline H. Johnson and Vasilis Vasiliou

Insights about genome function from spatial organization of the genome

Over the last 15 years, development of chromosome conformation capture (3C) and its subsequent high-throughput variants in conjunction with the fast development of sequencing technology has allowed investigato...

Authors: Shuvra Shekhar Roy, Ananda Kishore Mukherjee and Shantanu Chowdhury

APPLaUD: access for patients and participants to individual level uninterpreted genomic data

There is a growing support for the stance that patients and research participants should have better and easier access to their raw (uninterpreted) genomic sequence data in both clinical and research contexts.

Authors: Adrian Thorogood, Jason Bobe, Barbara Prainsack, Anna Middleton, Erick Scott, Sarah Nelson, Manuel Corpas, Natasha Bonhomme, Laura Lyman Rodriguez, Madeleine Murtagh and Erika Kleiderman

The genetic structure of the Belgian population

National and international efforts like the 1000 Genomes Project are leading to increasing insights in the genetic structure of populations worldwide. Variation between different populations necessitates acces...

Authors: Jimmy Van den Eynden, Tine Descamps, Els Delporte, Nancy H. C. Roosens, Sigrid C. J. De Keersmaecker, Vanessa De Wit, Joris Robert Vermeesch, Els Goetghebeur, Jean Tafforeau, Stefaan Demarest, Marc Van den Bulcke and Herman Van Oyen

Meeting report of the 2017 KidGen Renal Genetics Symposium

The 2017 KidGen Renal Genetics Symposium was held at the Royal Children’s Hospital and Murdoch Children’s Research Institute, Melbourne, from 6 to 8 December 2017. This meeting addressed clinical, diagnostic, ...

Authors: Kushani Jayasinghe, Cathy Quinlan, Zornitza Stark, Chirag Patel, Matthew G. Sampson, Moin Saleem and Andrew J. Mallett

Beyond genomics: understanding exposotypes through metabolomics

Over the past 20 years, advances in genomic technology have enabled unparalleled access to the information contained within the human genome. However, the multiple genetic variants associated with various dise...

Authors: Nicholas J. W. Rattray, Nicole C. Deziel, Joshua D. Wallach, Sajid A. Khan, Vasilis Vasiliou, John P. A. Ioannidis and Caroline H. Johnson

Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly

Whole-exome sequencing (WES) over the last few years has been increasingly employed for clinical diagnosis. However, one caveat with its use is that it inevitably fails to detect disease-causative variants that o...

Authors: Ye Wang, Xueli Wu, Liu Du, Ju Zheng, Songqing Deng, Xin Bi, Qiuyan Chen, Hongning Xie, Claude Férec, David N. Cooper, Yanmin Luo, Qun Fang and Jian-Min Chen

Identify Down syndrome transcriptome associations using integrative analysis of microarray database and correlation-interaction network

Long non-coding RNAs (lncRNAs) have previously been emerged as key players in a series of biological processes. Dysregulation of lncRNA is correlated to human diseases including neurological disorders. Here, w...

Authors: Min Chen, Jiayan Wang, Yingjun Luo, Kailing Huang, Xiaoshun Shi, Yanhui Liu, Jin Li, Zhengfei Lai, Shuya Xue, Haimei Gao, Allen Chen and Dunjin Chen

Ensemble genomic analysis in human lung tissue identifies novel genes for chronic obstructive pulmonary disease

Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) significantly associated with chronic obstructive pulmonary disease (COPD). However, many genetic variants show sug...

Authors: Jarrett D. Morrow, Michael H. Cho, John Platig, Xiaobo Zhou, Dawn L. DeMeo, Weiliang Qiu, Bartholome Celli, Nathaniel Marchetti, Gerard J. Criner, Raphael Bueno, George R. Washko, Kimberly Glass, John Quackenbush, Edwin K. Silverman and Craig P. Hersh

Overexpressed HSF1 cancer signature genes cluster in human chromosome 8q

HSF1 (heat shock factor 1) is a transcription factor that is found to facilitate malignant cancer development and proliferation. In cancer cells, HSF1 mediates a set of genes distinct from heat shock that cont...

Authors: Christopher Q. Zhang, Heinric Williams, Thomas L. Prince and Eric S. Ho

Early-life adversity and long-term neurobehavioral outcomes: epigenome as a bridge?

Accumulating evidence suggests that adversities at critical periods in early life, both pre- and postnatal, can lead to neuroendocrine perturbations, including hypothalamic-pituitary-adrenal axis dysregulation...

Authors: Alexander M. Vaiserman and Alexander K. Koliada

Correction to: Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism

After publication of the article [1], it has been brought to our attention that there is a nomenclature issue with this article. At the time of acceptance, the VARS2 mutation was considered equivalent to the V...

Authors: Abdulaziz Alsemari, Banan Al-Younes, Ewa Goljan, Dyala Jaroudi, Faisal BinHumaid, Brian F. Meyer, Stefan T. Arold and Dorota Monies

Yale school of public health symposium on lifetime exposures and human health: the exposome; summary and future reflections

The exposome is defined as “the totality of environmental exposures encountered from birth to death” and was developed to address the need for comprehensive environmental exposure assessment to better understa...

Authors: Caroline H. Johnson, Toby J. Athersuch, Gwen W. Collman, Suraj Dhungana, David F. Grant, Dean P. Jones, Chirag J. Patel and Vasilis Vasiliou

Ethical frameworks for obtaining informed consent in tumour profiling: an evidence-based case for Singapore

Genomic profiling of malignant tumours has assisted clinicians in providing targeted therapies for many serious cancer-related illnesses. Although the characterisation of somatic mutations is the primary aim o...

Authors: Yasmin Bylstra, Tamra Lysaght, Jyothi Thrivikraman, Sangeetha Watson and Patrick Tan

Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients

Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted...

Authors: Konstantinos Mitropoulos, Eleni Merkouri Papadima, Georgia Xiromerisiou, Angeliki Balasopoulou, Kyriaki Charalampidou, Vasiliki Galani, Krystallia-Vassiliki Zafeiri, Efthymios Dardiotis, Styliani Ralli, Georgia Deretzi, Anne John, Kyriaki Kydonopoulou, Elpida Papadopoulou, Alba di Pardo, Fulya Akcimen, Annalisa Loizedda…

The peptidylglycine-α-amidating monooxygenase (PAM) gene rs13175330 A>G polymorphism is associated with hypertension in a Korean population

Peptidylglycine-α-amidating monooxygenase (PAM) may play a role in the secretion of atrial natriuretic peptide (ANP), which is a hormone involved in the maintenance of blood pressure (BP). The objective of the...

Authors: Hye Jin Yoo, Minjoo Kim, Minkyung Kim, Jey Sook Chae, Sang-Hyun Lee and Jong Ho Lee

Recessive VARS2 mutation underlies a novel syndrome with epilepsy, mental retardation, short stature, growth hormone deficiency, and hypogonadism

Most mitochondrial and cytoplasmic aminoacyl-tRNA synthetases (aaRSs) are encoded by nuclear genes. Syndromic disorders resulting from mutation of aaRSs genes display significant phenotypic heterogeneity. We e...

Authors: Abdulaziz Alsemari, Banan Al-Younes, Ewa Goljan, Dyala Jaroudi, Faisal BinHumaid, Brian F. Meyer, Stefan T. Arold and Dorota Monies

Identification of functional single nucleotide polymorphisms in the branchpoint site

The human genome contains millions of single nucleotide polymorphisms (SNPs); many of these SNPs are intronic and have unknown functional significance. SNPs occurring within intron branchpoint sites, especiall...

Authors: Hung-Lun Chiang, Jer-Yuarn Wu and Yuan-Tsong Chen

Single nucleotide polymorphisms in the angiogenic and lymphangiogenic pathways are associated with lymphedema caused by Wuchereria bancrofti

Lymphedema (LE) is a chronic clinical manifestation of filarial nematode infections characterized by lymphatic dysfunction and subsequent accumulation of protein-rich fluid in the interstitial space—lymphatic ...

Authors: Linda Batsa Debrah, Anna Albers, Alexander Yaw Debrah, Felix F. Brockschmidt, Tim Becker, Christine Herold, Andrea Hofmann, Jubin Osei-Mensah, Yusif Mubarik, Holger Fröhlich, Achim Hoerauf and Kenneth Pfarr

Identification of a novel genetic locus underlying tremor and dystonia

Five affected individuals with syndromic tremulous dystonia, spasticity, and white matter disease from a consanguineous extended family covering a period of over 24 years are presented. A positional cloning ap...

Authors: Dorota Monies, Hussam Abou Al-Shaar, Ewa A. Goljan, Banan Al-Younes, Muna Monther Abdullah Al-Breacan, Maher Mohammed Al-Saif, Salma M. Wakil, Brian F. Meyer, Khalid S. A. Khabar and Saeed Bohlega

Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in β-type hemoglobinopathy patients

Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, i...

Authors: Vasiliki Chondrou, Petros Kolovos, Argyro Sgourou, Alexandra Kourakli, Alexia Pavlidaki, Vlasia Kastrinou, Anne John, Argiris Symeonidis, Bassam R. Ali, Adamantia Papachatzopoulou, Theodora Katsila and George P. Patrinos