Articles

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

Precision medicine at the crossroads

There are bioethical, institutional, economic, legal, and cultural obstacles to creating the robust-precompetitive-data resource that will be required to advance the vision of “precision medicine,” the ability...

Authors: Maynard V. Olson

Evaluating somatic tumor mutation detection without matched normal samples

Observations of recurrent somatic mutations in tumors have led to identification and definition of signaling and other pathways that are important for cancer progression and therapeutic targeting. As tumor cel...

Authors: Jamie K. Teer, Yonghong Zhang, Lu Chen, Eric A. Welsh, W. Douglas Cress, Steven A. Eschrich and Anders E. Berglund

Distinct transcriptional and metabolic profiles associated with empathy in Buddhist priests: a pilot study

Growing evidence suggests that spiritual/religious involvement may have beneficial effects on both psychological and physical functions. However, the biological basis for this relationship remains unclear. Thi...

Authors: Junji Ohnishi, Satoshi Ayuzawa, Seiji Nakamura, Shigeko Sakamoto, Miyo Hori, Tomoko Sasaoka, Eriko Takimoto-Ohnishi, Masakazu Tanatsugu and Kazuo Murakami

Falling giants and the rise of gene editing: ethics, private interests and the public good

This paper considers the tensions created in genomic research by public and private for-profit ideals. Our intent is to strengthen the public good at a time when doing science is strongly motivated by market p...

Authors: Benjamin Capps, Ruth Chadwick, Yann Joly, John J. Mulvihill, Tamra Lysaght and Hub Zwart

Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients

Osteogenesis imperfecta (OI) is a rare bone disorder. In 90% of cases, OI is caused by mutations in the COL1A1/2 genes, which code procollagen α1 and α2 chains. The main aim of the current research was to identif...

Authors: Lidiia Zhytnik, Katre Maasalu, Ene Reimann, Ele Prans, Sulev Kõks and Aare Märtson

A novel RLBP1 gene geographical area-related mutation present in a young patient with retinitis punctata albescens

Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopi...

Authors: Concetta Scimone, Luigi Donato, Teresa Esposito, Carmela Rinaldi, Rosalia D’Angelo and Antonina Sidoti

Long non-coding RNAs as novel players in β cell function and type 1 diabetes

Long non-coding RNAs (lncRNAs) are a sub-class within non-coding RNA repertoire that have emerged as crucial regulators of the gene expression in various pathophysiological conditions. lncRNAs display remarkab...

Authors: Aashiq H. Mirza, Simranjeet Kaur and Flemming Pociot

Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome

The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite th...

Authors: Benjamin M. Helm, Jason R. Willer, Azita Sadeghpour, Christelle Golzio, Eric Crouch, Samantha Schrier Vergano, Nicholas Katsanis and Erica E. Davis

Inferring clonal structure in HTLV-1-infected individuals: towards bridging the gap between analysis and visualization

Human T cell leukemia virus type 1 (HTLV-1) causes adult T cell leukemia (ATL) in a proportion of infected individuals after a long latency period. Development of ATL is a multistep clonal process that can be ...

Authors: Amir Farmanbar, Sanaz Firouzi, Wojciech Makałowski, Masako Iwanaga, Kaoru Uchimaru, Atae Utsunomiya, Toshiki Watanabe and Kenta Nakai

Development and validation of a variant detection workflow for BRCA1 and BRCA2 genes and its clinical application based on the Ion Torrent technology

Breast cancer is the most common among women worldwide, and ovarian cancer is the most difficult gynecological tumor to diagnose and with the lowest chance of cure. Mutations in BRCA1 and BRCA2 genes increase the...

Authors: Ana Lígia Buzolin, Caroline Mônaco Moreira, Patricia Rossi Sacramento, Andre Yuji Oku, Alexandre Ricardo dos Santos Fornari, David Santos Marco Antonio, Caio Robledo D Angioli Costa Quaio, Wagner Rosa Baratela and Miguel Mitne-Neto

The NF1 somatic mutational landscape in sporadic human cancers

Neurofibromatosis type 1 (NF1: Online Mendelian Inheritance in Man (OMIM) #162200) is an autosomal dominantly inherited tumour predisposition syndrome. Heritable constitutional mutations in the NF1 gene result in...

Authors: Charlotte Philpott, Hannah Tovell, Ian M. Frayling, David N. Cooper and Meena Upadhyaya

Genetic variation in neurodegenerative diseases and its accessibility in the model organism Caenorhabditis elegans

Neurodegenerative diseases (NGDs) such as Alzheimer’s and Parkinson’s are debilitating and largely untreatable conditions strongly linked to age. The clinical, neuropathological, and genetic components of NGDs...

Authors: Yiru Anning Wang, Jan Edward Kammenga and Simon Crawford Harvey

A pipeline combining multiple strategies for prioritizing heterozygous variants for the identification of candidate genes in exome datasets

The identification of disease-causing variants in autosomal dominant diseases using exome-sequencing data remains a difficult task in small pedigrees. We combined several strategies to improve filtering and pr...

Authors: Teresa Requena, Alvaro Gallego-Martinez and Jose A. Lopez-Escamez

Variant effect prediction tools assessed using independent, functional assay-based datasets: implications for discovery and diagnostics

Genetic variant effect prediction algorithms are used extensively in clinical genomics and research to determine the likely consequences of amino acid substitutions on protein function. It is vital that we bet...

Authors: Khalid Mahmood, Chol-hee Jung, Gayle Philip, Peter Georgeson, Jessica Chung, Bernard J. Pope and Daniel J. Park

Identification of novel genes associated with HIV-1 latency by analysis of histone modifications

A reservoir of HIV-1 is a major obstacle in eliminating HIV-1 in patients because it can reactivate in stopping antiretroviral therapy (ART). Histone modifications, such as acetylation and methylation, play a ...

Authors: Kyung-Chang Kim, Sunyoung Lee, Junseock Son, Younghyun Shin, Cheol-Hee Yoon, Chun Kang and Byeong-Sun Choi

Genome-wide DNA methylation analysis reveals hypomethylation in the low-CpG promoter regions in lymphoblastoid cell lines

Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types o...

Authors: Itsuki Taniguchi, Chihiro Iwaya, Keizo Ohnaka, Hiroki Shibata and Ken Yamamoto

In silico prioritization and further functional characterization of SPINK1 intronic variants

SPINK1 (serine protease inhibitor, kazal-type, 1), which encodes human pancreatic secretory trypsin inhibitor, is one of the most extensively studied genes underlying chronic pancreati...

Authors: Wen-Bin Zou, Hao Wu, Arnaud Boulling, David N. Cooper, Zhao-Shen Li, Zhuan Liao, Jian-Min Chen and Claude Férec

Whole-exome sequencing identifies novel candidate predisposition genes for familial polycythemia vera

Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe),...

Authors: Elina A. M. Hirvonen, Esa Pitkänen, Kari Hemminki, Lauri A. Aaltonen and Outi Kilpivaara

The Israeli National Genetic database: a 10-year experience

The Israeli National and Ethnic Mutation database (http://​server.​goldenhelix.​org/​israeli) was launched in September 2006 on the ETHNOS software to incl...

Authors: Joël Zlotogora and George P. Patrinos

Transcriptome analysis of bronchoalveolar lavage fluid from children with severe Mycoplasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency

A growing number of severe Mycoplasma pneumoniae pneumonia (MPP) cases have been reported recently. However, the pathogenesis of severe MPP is not clear. In the current study, transcriptome sequencing was used to...

Authors: Kuo Wang, Man Gao, Mingyue Yang, Fanzheng Meng, Deli Li, Ruihua Lu, Yan Wang, Huadong Zhuang, Mengyao Li, Genhong Cheng and Xiaosong Wang

Genetic determinants of clinical heterogeneity of the coronary artery disease in the population of Hyderabad, India

Genetic predisposition to the clinical categories of coronary artery disease (anatomical viz., insignificant, single, double, and triple vessel diseases and phenotypic severity categories viz., angina, acute c...

Authors: Rayabarapu Pranavchand, Arramraju Sreenivas Kumar and Battini Mohan Reddy

Copy number variation of human AMY1 is a minor contributor to variation in salivary amylase expression and activity

Salivary amylase in humans is encoded by the copy variable gene AMY1 in the amylase gene cluster on chromosome 1. Although the role of salivary amylase is well established, the consequences of the copy number var...

Authors: Danielle Carpenter, Laura M. Mitchell and John A. L. Armour

Variants in congenital hypogonadotrophic hypogonadism genes identified in an Indonesian cohort of 46,XY under-virilised boys

Congenital hypogonadotrophic hypogonadism (CHH) and Kallmann syndrome (KS) are caused by disruption to the hypothalamic-pituitary-gonadal (H-P-G) axis. In particular, reduced production, secretion or action of...

Authors: Katie L. Ayers, Aurore Bouty, Gorjana Robevska, Jocelyn A. van den Bergen, Achmad Zulfa Juniarto, Nurin Aisyiyah Listyasari, Andrew H. Sinclair and Sultana M. H. Faradz

The status of Her2 amplification and Kras mutations in mucinous ovarian carcinoma

Jayson GC et al. remarked in Lancet that nearly 100% of mucinous ovarian cancer cases have Kras mutation as well as a high frequency of Her2 amplification. Using the Abbott PathVysion Her2 DNA Probe Kit and Kras ...

Authors: Kuang-Leei Chang, Ming-Yung Lee, Wan-Ru Chao and Chih-Ping Han

Head-and-neck squamous cell carcinoma risk in smokers: no association detected between phenotype and AHR, CYP1A1, CYP1A2, or CYP1B1 genotype

Head-and-neck squamous cell carcinoma (HNSCC) differs between smokers and nonsmokers in etiology and clinical presentation. Because of demonstrated unequivocal involvement in smoking-induced cancer in laborato...

Authors: Lucia F. Jorge-Nebert, Ge Zhang, Keith M. Wilson, Zhengwen Jiang, Randall Butler, Jack L. Gluckman, Susan M. Pinney and Daniel W. Nebert

Targeted next generation sequencing identifies novel NOTCH3 gene mutations in CADASIL diagnostics patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic, hereditary, small vessel disease of the brain causing stroke and vascular dementia in adults...

Authors: Neven Maksemous, Robert A. Smith, Larisa M. Haupt and Lyn R. Griffiths

Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive loss of renal function in adults as a consequence of the accumulation of cysts. ADPKD is the most common genetic cause of end-stage renal...

Authors: Rita M. C. de Almeida, Sherry G. Clendenon, William G. Richards, Michael Boedigheimer, Michael Damore, Sandro Rossetti, Peter C. Harris, Britney-Shea Herbert, Wei Min Xu, Angela Wandinger-Ness, Heather H. Ward, James A. Glazier and Robert L. Bacallao

A genomic case study of desmoplastic small round cell tumor: comprehensive analysis reveals insights into potential therapeutic targets and development of a monitoring tool for a rare and aggressive disease

Genome-wide profiling of rare tumors is crucial for improvement of diagnosis, treatment, and, consequently, achieving better outcomes. Desmoplastic small round cell tumor (DSRCT) is a rare type of sarcoma aris...

Authors: Elisa Napolitano Ferreira, Bruna Durães Figueiredo Barros, Jorge Estefano de Souza, Renan Valieris Almeida, Giovana Tardin Torrezan, Sheila Garcia, Ana Cristina Victorino Krepischi, Celso Abdon Lopes de Mello, Isabela Werneck da Cunha, Clóvis Antonio Lopes Pinto, Fernando Augusto Soares, Emmanuel Dias-Neto, Ademar Lopes, Sandro José de Souza and Dirce Maria Carraro