Articles

A review of the new HGNC gene family resource

The HUGO Gene Nomenclature Committee (HGNC) approves unique gene symbols and names for human loci. As well as naming genomic loci, we manually curate genes into family sets based on shared characteristics such...

Authors: Kristian A Gray, Ruth L Seal, Susan Tweedie, Mathew W Wright and Elspeth A Bruford

Erratum to: Copy number variation in CEP57L1 predisposes to congenital absence of bilateral ACL and PCL ligaments

Authors: Yichuan Liu, Yun Li, Michael E. March, Kenny Nguyen, Kexiang Xu, Fengxiang Wang, Yiran Guo, Brendan Keating, Joseph Glessner, Jiankang Li, Theodore J. Ganley, Jianguo Zhang, Matthew A. Deardorff, Xun Xu and Hakon Hakonarson

The clinical trial landscape in oncology and connectivity of somatic mutational profiles to targeted therapies

Precision medicine in oncology relies on rapid associations between patient-specific variations and targeted therapeutic efficacy. Due to the advancement of genomic analysis, a vast literature characterizing c...

Authors: Sara E. Patterson, Rangjiao Liu, Cara M. Statz, Daniel Durkin, Anuradha Lakshminarayana and Susan M. Mockus

Genetic studies of Polish migraine patients: screening for causative mutations in four migraine-associated genes

Migraine is the most common neurological disorder, affecting approximately 12 % of the adult population worldwide, caused by both environmental and genetic factors. Three causative genes have been identified i...

Authors: Izabela Domitrz, Michalina Kosiorek, Cezary Żekanowski and Anna Kamińska

Intragraft transcriptional profiling of renal transplant patients with tubular dysfunction reveals mechanisms underlying graft injury and recovery

Proximal tubular dysfunction (PTD) is associated with a decreased long-term graft survival in renal transplant patients and can be detected by the elevation of urinary tubular proteins. This study investigated...

Authors: Hátylas Azevedo, Paulo Guilherme Renesto, Rogério Chinen, Erika Naka, Ana Cristina Carvalho de Matos, Marcos Antônio Cenedeze, Carlos Alberto Moreira-Filho, Niels Olsen Saraiva Câmara and Alvaro Pacheco-Silva

Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility

Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15–20 % smokers manifest...

Authors: Shannon Bruse, Michael Moreau, Yana Bromberg, Jun-Ho Jang, Nan Wang, Hongseok Ha, Maria Picchi, Yong Lin, Raymond J. Langley, Clifford Qualls, Julia Klensney-Tait, Joseph Zabner, Shuguang Leng, Jenny Mao, Steven A. Belinsky, Jinchuan Xing…

Integrative genomic analysis reveals functional diversification of APOBEC gene family in breast cancer

The human APOBEC protein family plays critical but distinct roles in host defense. Recent studies revealed that APOBECs mediate C-to-T mutagenesis in multiple cancers, including breast cancer. It is still uncl...

Authors: Yanfeng Zhang, Ryan Delahanty, Xingyi Guo, Wei Zheng and Jirong Long

Next-generation sequencing using a pre-designed gene panel for the molecular diagnosis of congenital disorders in pediatric patients

Next-generation sequencing (NGS) has revolutionized genetic research and offers enormous potential for clinical application. Sequencing the exome has the advantage of casting the net wide for all known coding ...

Authors: Eileen C. P. Lim, Maggie Brett, Angeline H. M. Lai, Siew-Peng Lee, Ee-Shien Tan, Saumya S. Jamuar, Ivy S. L. Ng and Ene-Choo Tan

Update of the human and mouse Fanconi anemia genes

Fanconi anemia (FA) is a recessively inherited disease manifesting developmental abnormalities, bone marrow failure, and increased risk of malignancies. Whereas FA has been studied for nearly 90 years, only in...

Authors: Hongbin Dong, Daniel W. Nebert, Elspeth A. Bruford, David C. Thompson, Hans Joenje and Vasilis Vasiliou

Copy number variation in CEP57L1 predisposes to congenital absence of bilateral ACL and PCL ligaments

Absence of the anterior (ACL) or posterior cruciate ligament (PCL) are rare congenital malformations that result in knee joint instability, with a prevalence of 1.7 per 100,000 live births and can be associate...

Authors: Yichuan Liu, Yun Li, Michael E. March, Kenny Nguyen, Kexiang Xu, Fengxiang Wang, Yiran Guo, Brendan Keating, Joseph Glessner, Jiankang Li, Theodore J. Ganley, Jianguo Zhang, Matthew A. Deardorff, Xun Xu and Hakon Hakonarson

HDAC3 role in medication consumption in medication overuse headache patients: a pilot study

Medication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or oth...

Authors: Claudia Pisanu, Stefano Caproni, Donatella Congiu, Letizia M. Cupini, Alessio Squassina, George P. Patrinos, Ilenia Corbelli, Paolo Calabresi, Maria Del Zompo and Paola Sarchielli

Genomics is changing personal healthcare and medicine: the dawn of iPH (individualized preventive healthcare)

This opinion piece focuses on the convergence of information technology (IT) in the form of personal monitors, especially smart phones and possibly also smart watches, individual genomic information and preven...

Authors: Ruty Mehrian-Shai and Juergen K. V. Reichardt

A survey of computational tools for downstream analysis of proteomic and other omic datasets

Proteomics is an expanding area of research into biological systems with significance for biomedical and therapeutic applications ranging from understanding the molecular basis of diseases to testing new treat...

Authors: Anis Karimpour-Fard, L. Elaine Epperson and Lawrence E. Hunter

Cancer classification in the genomic era: five contemporary problems

Classification is an everyday instinct as well as a full-fledged scientific discipline. Throughout the history of medicine, disease classification is central to how we develop knowledge, make diagnosis, and as...

Authors: Qingxuan Song, Sofia D. Merajver and Jun Z. Li

Integrative DNA methylation and gene expression analysis to assess the universality of the CpG island methylator phenotype

The CpG island methylator phenotype (CIMP) was first characterized in colorectal cancer but since has been extensively studied in several other tumor types such as breast, bladder, lung, and gastric. CIMP is o...

Authors: Matahi Moarii, Fabien Reyal and Jean-Philippe Vert

Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that t...

Authors: Mary B. Mayes, Taniesha Morgan, Jincy Winston, Daniel S. Buxton, Mihir Anant Kamat, Debbie Smith, Maggie Williams, Rebecca L. Martin, Dirk A. Kleinjan, David N. Cooper, Meena Upadhyaya and Nadia Chuzhanova

Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities

“CCN” is an acronym referring to the first letter of each of the first three members of this original group of mammalian functionally and phylogenetically distinct extracellular matrix (ECM) proteins [i.e., cy...

Authors: Izabela Krupska, Elspeth A. Bruford and Brahim Chaqour

MATWIN: bridging the gap between academic research and industry

MATWIN (Maturation and Accelerating Translation With INdustry) is part of the nationwide effort to support cancer innovation. This unique program is willing to support innovative research projects providing to...

Authors: Josy Reiffers and Lucia Robert

Copy number alterations detected by whole-exome and whole-genome sequencing of esophageal adenocarcinoma

Esophageal adenocarcinoma (EA) is among the leading causes of cancer mortality, especially in developed countries. A high level of somatic copy number alterations (CNAs) accumulates over the decades in the pro...

Authors: Xiaoyu Wang, Xiaohong Li, Yichen Cheng, Xin Sun, Xibin Sun, Steve Self, Charles Kooperberg and James Y. Dai

Trans-species polymorphism in humans and the great apes is generally maintained by balancing selection that modulates the host immune response

Known examples of ancient identical-by-descent genetic variants being shared between evolutionarily related species, known as trans-species polymorphisms (TSPs), result from counterbalancing selective forces a...

Authors: Luisa Azevedo, Catarina Serrano, Antonio Amorim and David N. Cooper

Performance evaluation of indel calling tools using real short-read data

Insertion and deletion (indel), a common form of genetic variation, has been shown to cause or contribute to human genetic diseases and cancer. With the advance of next-generation sequencing technology, many i...

Authors: Mohammad Shabbir Hasan, Xiaowei Wu and Liqing Zhang

Whole-genome sequencing targets drug-resistant bacterial infections

During the past two decades, the technological progress of whole-genome sequencing (WGS) had changed the fields of Environmental Microbiology and Biotechnology, and, currently, is changing the underlying princ...

Authors: N. V. Punina, N. M. Makridakis, M. A. Remnev and A. F. Topunov

Predicting the combined effect of multiple genetic variants

Many genetic variants have been identified in the human genome. The functional effects of a single variant have been intensively studied. However, the joint effects of multiple variants in the same genes have ...

Authors: Mingming Liu, Layne T. Watson and Liqing Zhang

Epigenetic inheritance and the missing heritability

Genome-wide association studies of complex physiological traits and diseases consistently found that associated genetic factors, such as allelic polymorphisms or DNA mutations, only explained a minority of the...

Authors: Marco Trerotola, Valeria Relli, Pasquale Simeone and Saverio Alberti

Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies

Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated th...

Authors: Boon-Peng Hoh, Lian Deng, Mat Jusoh Julia-Ashazila, Zakaria Zuraihan, Ma’amor Nur-Hasnah, Ab Rajab Nur‐Shafawati, Wan Isa Hatin, Ismail Endom, Bin Alwi Zilfalil, Yusoff Khalid and Shuhua Xu

Utility and limitations of exome sequencing as a genetic diagnostic tool for conditions associated with pediatric sudden cardiac arrest/sudden cardiac death

Conditions associated with sudden cardiac arrest/death (SCA/D) in youth often have a genetic etiology. While SCA/D is uncommon, a pro-active family screening approach may identify these inherited structural an...

Authors: Mindy H. Li, Jenica L. Abrudan, Matthew C. Dulik, Ariella Sasson, Joshua Brunton, Vijayakumar Jayaraman, Noreen Dugan, Danielle Haley, Ramakrishnan Rajagopalan, Sawona Biswas, Mahdi Sarmady, Elizabeth T. DeChene, Matthew A. Deardorff, Alisha Wilkens, Sarah E. Noon, Maria I. Scarano…

SIRT1 affects DNA methylation of polycomb group protein target genes, a hotspot of the epigenetic shift observed in ageing

SIRT1 is likely to play a role in the extension in healthspan induced by dietary restriction. Actions of SIRT1 are pleiotropic, and effects on healthspan may include effects on DNA methylation. Polycomb group ...

Authors: Luisa A Wakeling, Laura J Ions, Suzanne M Escolme, Simon J Cockell, Tianhong Su, Madhurima Dey, Emily V Hampton, Gail Jenkins, Linda J Wainwright, Jill A McKay and Dianne Ford

Genomics in the renal clinic - translating nephrogenetics for clinical practice

Genetic Renal Disease (GRD) presents to mainstream clinicians as a mixture of kidney-specific as well as multi-organ entities, many with highly variable phenotype-genotype relationships. The rapid increase in ...

Authors: Andrew Mallett, Christopher Corney, Hugh McCarthy, Stephen I. Alexander and Helen Healy

Identification of cancer predisposition variants in apparently healthy individuals using a next-generation sequencing-based family genomics approach

Cancer, like many common disorders, has a complex etiology, often with a strong genetic component and with multiple environmental factors contributing to susceptibility. A considerable number of genomic varian...

Authors: Ioannis Karageorgos, Clint Mizzi, Efstathia Giannopoulou, Cristiana Pavlidis, Brock A. Peters, Zoi Zagoriti, Peter D. Stenson, Konstantinos Mitropoulos, Joseph Borg, Haralabos P. Kalofonos, Radoje Drmanac, Andrew Stubbs, Peter van der Spek, David N. Cooper, Theodora Katsila and George P. Patrinos

Success stories in genomic medicine from resource-limited countries

In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major dis...

Authors: Konstantinos Mitropoulos, Hayat Al Jaibeji, Diego A. Forero, Paul Laissue, Ambroise Wonkam, Catalina Lopez-Correa, Zahurin Mohamed, Wasun Chantratita, Ming Ta Michael Lee, Adrian Llerena, Angela Brand, Bassam R. Ali and George P. Patrinos

Clinical application of next-generation sequencing for Mendelian diseases

Over the past decade, next-generation sequencing (NGS) has led to an exponential increase in our understanding of the genetic basis of Mendelian diseases. NGS allows for the analysis of multiple regions of the...

Authors: Saumya Shekhar Jamuar and Ene-Choo Tan

Is the genomic translational pipeline being disrupted?

The translational pipeline for genomic medicine has been well defined. However, as with any rapidly changing technology, innovations are difficult to predict leading to the potential to disrupt anticipated tra...

Authors: Marc S. Williams

Prediction of complex human diseases from pathway-focused candidate markers by joint estimation of marker effects: case of chronic fatigue syndrome

The current practice of using only a few strongly associated genetic markers in regression models results in generally low power in prediction or accounting for heritability of complex human traits.

Authors: Madhuchhanda Bhattacharjee, Mangalathu S. Rajeevan and Mikko J. Sillanpää

Complement regulator CD46: genetic variants and disease associations

Membrane cofactor protein (MCP; CD46) is an ubiquitously expressed complement regulatory protein that protects host cells from injury by complement. This type-I membrane glycoprotein serves as a cofactor for t...

Authors: M. Kathryn Liszewski and John P. Atkinson

Whole-exome sequencing identifies de novo mutation in the COL1A1 gene to underlie the severe osteogenesis imperfecta

Osteogenesis imperfecta (OI) comprises a clinically and genetically heterogeneous group of connective tissue disorders, characterized by low bone mass, increased bone fragility, and blue-gray eye sclera. OI of...

Authors: Katre Maasalu, Tiit Nikopensius, Sulev Kõks, Margit Nõukas, Mart Kals, Ele Prans, Lidiia Zhytnik, Andres Metspalu and Aare Märtson

Comparative sequence- and structure-inspired drug design for PilF protein of Neisseria meningitidis

Serogroup A of Neisseria meningitidis is the organism responsible for causing epidemic diseases in developing countries by a pilus-mediated adhesion to human brain endothelial cells. Type IV pilus assembly protei...

Authors: Abijeet Singh Mehta, Kirti Snigdha, M Sharada Potukuchi and Panagiotis A Tsonis

Reviewer acknowledgement 2015

The Editors of Human Genomics would like to thank all our reviewers who have contributed to the journal in volume 8 (2014).

Authors: Vasilis Vasiliou

Evaluation of copy number variation and gene expression in neurofibromatosis type-1-associated malignant peripheral nerve sheath tumours

Neurofibromatosis type-1 (NF1) is a complex neurogenetic disorder characterised by the development of benign and malignant tumours of the peripheral nerve sheath (MPNSTs). Whilst biallelic NF1 gene inactivation c...

Authors: Laura E Thomas, Jincy Winston, Ellie Rad, Matthew Mort, Kayleigh M Dodd, Andrew R Tee, Fionnuala McDyer, Stephen Moore, David N Cooper and Meena Upadhyaya

Rapid detection of genetic mutations in individual breast cancer patients by next-generation DNA sequencing

Breast cancer is the most common malignancy in women and the leading cause of cancer deaths in women worldwide. Breast cancers are heterogenous and exist in many different subtypes (luminal A, luminal B, tripl...

Authors: Suqin Liu, Hongjiang Wang, Lizhi Zhang, Chuanning Tang, Lindsey Jones, Hua Ye, Liying Ban, Aman Wang, Zhiyuan Liu, Feng Lou, Dandan Zhang, Hong Sun, Haichao Dong, Guangchun Zhang, Zhishou Dong, Baishuai Guo…

Self-reported race/ethnicity in the age of genomic research: its potential impact on understanding health disparities

This review explores the limitations of self-reported race, ethnicity, and genetic ancestry in biomedical research. Various terminologies are used to classify human differences in genomic research including ra...

Authors: Tesfaye B Mersha and Tilahun Abebe

Molecular signatures that correlate with induction of lens regeneration in newts: lessons from proteomic analysis

Amphibians have the remarkable ability to regenerate missing body parts. After complete removal of the eye lens, the dorsal but not the ventral iris will transdifferentiate to regenerate an exact replica of th...

Authors: Konstantinos Sousounis, Rital Bhavsar, Mario Looso, Marcus Krüger, Jessica Beebe, Thomas Braun and Panagiotis A Tsonis

Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data

Osteosarcoma (OS) is a prevalent primary malignant bone tumour with unknown etiology. These highly metastasizing tumours are among the most frequent causes of cancer-related deaths. Thus, there is an urgent ne...

Authors: Ene Reimann, Sulev Kõks, Xuan Dung Ho, Katre Maasalu and Aare Märtson

Survival analysis tools in genomics research

There is an increasing demand to determine the clinical implication of experimental findings in molecular biomedical research. Survival (or failure time) analysis methodologies have been adapted to the analysi...

Authors: Xintong Chen, Xiaochen Sun and Yujin Hoshida

Exome sequencing identifies novel and recurrent mutations in GJA8 and CRYGDassociated with inherited cataract

Inherited cataract is a clinically important and genetically heterogeneous cause of visual impairment. Typically, it presents at an early age with or without other ocular/systemic signs and lacks clear phenoty...

Authors: Donna S Mackay, Thomas M Bennett, Susan M Culican and Alan Shiels

Informed consent and ethical re-use of African genomic data

Rapid advances in human genomic research are increasing the availability of genomic data for secondary analysis. Particularly in the case of vulnerable African populations, ethics and informed consent processe...

Authors: Galen EB Wright, Adebowale A Adeyemo and Nicki Tiffin

Disease pathways at the Rat Genome Database Pathway Portal: genes in context-a network approach to understanding the molecular mechanisms of disease

Biological systems are exquisitely poised to respond and adjust to challenges, including damage. However, sustained damage can overcome the ability of the system to adjust and result in a disease phenotype, it...

Authors: Victoria Petri, G Thomas Hayman, Marek Tutaj, Jennifer R Smith, Stanley JF Laulederkind, Shur-Jen Wang, Rajni Nigam, Jeff De Pons, Mary Shimoyama, Melinda R Dwinell, Elizabeth A Worthey and Howard J Jacob

Improved drug therapy: triangulating phenomics with genomics and metabolomics

Embracing the complexity of biological systems has a greater likelihood to improve prediction of clinical drug response. Here we discuss limitations of a singular focus on genomics, epigenomics, proteomics, tr...

Authors: Andrew A Monte, Chad Brocker, Daniel W Nebert, Frank J Gonzalez, David C Thompson and Vasilis Vasiliou

Ethical issues in genomic research on the African continent: experiences and challenges to ethics review committees

This is a report on a workshop titled ‘Ethics for genomic research across five African countries: Guidelines, experiences and challenges’, University of the Witwatersrand, Johannesburg, South Africa, 10 and 11...

Authors: Michèle Ramsay, Jantina de Vries, Himla Soodyall, Shane A Norris and Osman Sankoh

Mixture models for gene expression experiments with two species

Cross-species research in drug development is novel and challenging. A bivariate mixture model utilizing information across two species was proposed to solve the fundamental problem of identifying differential...

Authors: Yuhua Su, Lei Zhu, Alan Menius and Jason Osborne

Validation and assessment of variant calling pipelines for next-generation sequencing

The processing and analysis of the large scale data generated by next-generation sequencing (NGS) experiments is challenging and is a burgeoning area of new methods development. Several new bioinformatics tool...

Authors: Mehdi Pirooznia, Melissa Kramer, Jennifer Parla, Fernando S Goes, James B Potash, W Richard McCombie and Peter P Zandi