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The Biology of Human Diseases, as Revealed Through Genomics

Guest Editors: Daniel MacArthur and Mark McCarthy

We are entering an era where the discovery of disease genes is conducted at the genome scale, and where integration of multiple types of ‘big data’ is used to elucidate variant-phenotype correlations. Additionally, a growing number of studies are identifying considerable overlap between common and rare human diseases, and further refining our understanding of their biology and the mechanisms by which they develop.

Genome Biology highlights important advances in human disease genomics with a special issue showcasing important work in this area.

  1. Review

    Multi-omics approaches to disease

    High-throughput technologies have revolutionized medical research. The advent of genotyping arrays enabled large-scale genome-wide association studies and methods for examining global transcript levels, which ...

    Yehudit Hasin, Marcus Seldin and Aldons Lusis

    Genome Biology 2017 18:83

    Published on: 5 May 2017

  2. Method

    cepip: context-dependent epigenomic weighting for prioritization of regulatory variants and disease-associated genes

    It remains challenging to predict regulatory variants in particular tissues or cell types due to highly context-specific gene regulation. By connecting large-scale epigenomic profiles to expression quantitativ...

    Mulin Jun Li, Miaoxin Li, Zipeng Liu, Bin Yan, Zhicheng Pan, Dandan Huang, Qian Liang, Dingge Ying, Feng Xu, Hongcheng Yao, Panwen Wang, Jean-Pierre A. Kocher, Zhengyuan Xia, Pak Chung Sham, Jun S. Liu and Junwen Wang

    Genome Biology 2017 18:52

    Published on: 16 March 2017

  3. Research

    Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes

    Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure of enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within the dista...

    Hongsheng Gui, Duco Schriemer, William W. Cheng, Rajendra K. Chauhan, Guillermo Antiňolo, Courtney Berrios, Marta Bleda, Alice S. Brooks, Rutger W. W. Brouwer, Alan J. Burns, Stacey S. Cherny, Joaquin Dopazo, Bart J. L. Eggen, Paola Griseri, Binta Jalloh, Thuy-Linh Le…

    Genome Biology 2017 18:48

    Published on: 8 March 2017

  4. Research

    Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome

    Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies.

    Ryan L. Collins, Harrison Brand, Claire E. Redin, Carrie Hanscom, Caroline Antolik, Matthew R. Stone, Joseph T. Glessner, Tamara Mason, Giulia Pregno, Naghmeh Dorrani, Giorgia Mandrile, Daniela Giachino, Danielle Perrin, Cole Walsh, Michelle Cipicchio, Maura Costello…

    Genome Biology 2017 18:36

    Published on: 6 March 2017

  5. Editorial

    Human disease genomics: from variants to biology

    We summarize the remarkable progress that has been made in the identification and functional characterization of DNA sequence variants associated with disease.

    Mark I. McCarthy and Daniel G. MacArthur

    Genome Biology 2017 18:20

    Published on: 30 January 2017

  6. Research

    Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing

    Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson’s disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated pa...

    Iris E. Jansen, Hui Ye, Sasja Heetveld, Marie C. Lechler, Helen Michels, Renée I. Seinstra, Steven J. Lubbe, Valérie Drouet, Suzanne Lesage, Elisa Majounie, J. Raphael Gibbs, Mike A. Nalls, Mina Ryten, Juan A. Botia, Jana Vandrovcova, Javier Simon-Sanchez…

    Genome Biology 2017 18:22

    Published on: 30 January 2017

  7. Research

    Integrated genome-wide analysis of expression quantitative trait loci aids interpretation of genomic association studies

    Identification of single nucleotide polymorphisms (SNPs) associated with gene expression levels, known as expression quantitative trait loci (eQTLs), may improve understanding of the functional role of phenoty...

    Roby Joehanes, Xiaoling Zhang, Tianxiao Huan, Chen Yao, Sai-xia Ying, Quang Tri Nguyen, Cumhur Yusuf Demirkale, Michael L. Feolo, Nataliya R. Sharopova, Anne Sturcke, Alejandro A. Schäffer, Nancy Heard-Costa, Han Chen, Po-ching Liu, Richard Wang, Kimberly A. Woodhouse…

    Genome Biology 2017 18:16

    Published on: 25 January 2017

  8. Research

    Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus

    In 2014, Western Africa experienced an unanticipated explosion of Ebola virus infections. What distinguishes fatal from non-fatal outcomes remains largely unknown, yet is key to optimising personalised treatme...

    Xuan Liu, Emily Speranza, César Muñoz-Fontela, Sam Haldenby, Natasha Y. Rickett, Isabel Garcia-Dorival, Yongxiang Fang, Yper Hall, Elsa-Gayle Zekeng, Anja Lüdtke, Dong Xia, Romy Kerber, Ralf Krumkamp, Sophie Duraffour, Daouda Sissoko, John Kenny…

    Genome Biology 2017 18:4

    Published on: 19 January 2017

  9. Method

    iRegNet3D: three-dimensional integrated regulatory network for the genomic analysis of coding and non-coding disease mutations

    The mechanistic details of most disease-causing mutations remain poorly explored within the context of regulatory networks. We present a high-resolution three-dimensional integrated regulatory network (iRegNet...

    Siqi Liang, Nathaniel D. Tippens, Yaoda Zhou, Matthew Mort, Peter D. Stenson, David N. Cooper and Haiyuan Yu

    Genome Biology 2017 18:10

    Published on: 18 January 2017

  10. Method

    GAVIN: Gene-Aware Variant INterpretation for medical sequencing

    We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele freque...

    K. Joeri van der Velde, Eddy N. de Boer, Cleo C. van Diemen, Birgit Sikkema-Raddatz, Kristin M. Abbott, Alain Knopperts, Lude Franke, Rolf H. Sijmons, Tom J. de Koning, Cisca Wijmenga, Richard J. Sinke and Morris A. Swertz

    Genome Biology 2017 18:6

    Published on: 16 January 2017

  11. Research

    Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery

    The relationship between monogenic and polygenic forms of epilepsy is poorly understood and the extent to which the genetic and acquired epilepsies share common pathways is unclear. Here, we use an integrated ...

    Andree Delahaye-Duriez, Prashant Srivastava, Kirill Shkura, Sarah R. Langley, Liisi Laaniste, Aida Moreno-Moral, Bénédicte Danis, Manuela Mazzuferi, Patrik Foerch, Elena V. Gazina, Kay Richards, Steven Petrou, Rafal M. Kaminski, Enrico Petretto and Michael R. Johnson

    Genome Biology 2016 17:245

    Published on: 13 December 2016

  12. Method

    DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases

    Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inf...

    Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler…

    Genome Biology 2016 17:255

    Published on: 12 December 2016

  13. Research

    Systematic analysis of chromatin interactions at disease associated loci links novel candidate genes to inflammatory bowel disease

    Genome-wide association studies (GWAS) have revealed many susceptibility loci for complex genetic diseases. For most loci, the causal genes have not been identified. Currently, the identification of candidate ...

    Claartje A. Meddens, Magdalena Harakalova, Noortje A. M. van den Dungen, Hassan Foroughi Asl, Hemme J. Hijma, Edwin P. J. G. Cuppen, Johan L. M. Björkegren, Folkert W. Asselbergs, Edward E. S. Nieuwenhuis and Michal Mokry

    Genome Biology 2016 17:247

    Published on: 30 November 2016

  14. Research

    Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans

    The 2’-5’ oligoadenylate synthetase (OAS) locus encodes for three OAS enzymes (OAS1-3) involved in innate immune response. This region harbors high amounts of Neandertal ancestry in non-African populations; ye...

    Aaron J. Sams, Anne Dumaine, Yohann Nédélec, Vania Yotova, Carolina Alfieri, Jerome E. Tanner, Philipp W. Messer and Luis B. Barreiro

    Genome Biology 2016 17:246

    Published on: 29 November 2016

  15. Research

    Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort

    Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients recei...

    Stefanie Eggers, Simon Sadedin, Jocelyn A. van den Bergen, Gorjana Robevska, Thomas Ohnesorg, Jacqueline Hewitt, Luke Lambeth, Aurore Bouty, Ingrid M. Knarston, Tiong Yang Tan, Fergus Cameron, George Werther, John Hutson, Michele O’Connell, Sonia R. Grover, Yves Heloury…

    Genome Biology 2016 17:243

    Published on: 29 November 2016

  16. Research

    Characterizing the morbid genome of ciliopathies

    Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge...

    Ranad Shaheen, Katarzyna Szymanska, Basudha Basu, Nisha Patel, Nour Ewida, Eissa Faqeih, Amal Al Hashem, Nada Derar, Hadeel Alsharif, Mohammed A. Aldahmesh, Anas M. Alazami, Mais Hashem, Niema Ibrahim, Firdous M. Abdulwahab, Rawda Sonbul, Hisham Alkuraya…

    Genome Biology 2016 17:242

    Published on: 28 November 2016

  17. Research

    Revisiting the morbid genome of Mendelian disorders

    The pathogenicity of many Mendelian variants has been challenged by large-scale sequencing efforts. However, many rare and benign “disease mutations” are difficult to analyze due to their rarity. The Saudi Ara...

    Mohamed Abouelhoda, Tariq Faquih, Mohamed El-Kalioby and Fowzan S. Alkuraya

    Genome Biology 2016 17:235

    Published on: 24 November 2016

  18. Research

    Whole genome sequence analysis of serum amino acid levels

    Blood levels of amino acids are important biomarkers of disease and are influenced by synthesis, protein degradation, and gene–environment interactions. Whole genome sequence analysis of amino acid levels may ...

    Bing Yu, Paul S. de Vries, Ginger A. Metcalf, Zhe Wang, Elena V. Feofanova, Xiaoming Liu, Donna Marie Muzny, Lynne E. Wagenknecht, Richard A. Gibbs, Alanna C. Morrison and Eric Boerwinkle

    Genome Biology 2016 17:237

    Published on: 24 November 2016

  19. Opinion

    The continuum of causality in human genetic disorders

    Studies of human genetic disorders have traditionally followed a reductionist paradigm. Traits are defined as Mendelian or complex based on family pedigree and population data, whereas alleles are deemed rare,...

    Nicholas Katsanis

    Genome Biology 2016 17:233

    Published on: 17 November 2016

  20. Research

    Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23

    The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potentia...

    Amanda McGovern, Stefan Schoenfelder, Paul Martin, Jonathan Massey, Kate Duffus, Darren Plant, Annie Yarwood, Arthur G. Pratt, Amy E. Anderson, John D. Isaacs, Julie Diboll, Nishanthi Thalayasingam, Caroline Ospelt, Anne Barton, Jane Worthington, Peter Fraser…

    Genome Biology 2016 17:212

    Published on: 1 November 2016

  21. Research

    GNB5 mutation causes a novel neuropsychiatric disorder featuring attention deficit hyperactivity disorder, severely impaired language development and normal cognition

    Neuropsychiatric disorders are common forms of disability in humans. Despite recent progress in deciphering the genetics of these disorders, their phenotypic complexity continues to be a major challenge. Mende...

    Hanan E. Shamseldin, Ikuo Masuho, Ahmed Alenizi, Suad Alyamani, Dipak N. Patil, Niema Ibrahim, Kirill A. Martemyanov and Fowzan S. Alkuraya

    Genome Biology 2016 17:195

    Published on: 27 September 2016

  22. Research

    An integrated genetic-epigenetic analysis of schizophrenia: evidence for co-localization of genetic associations and differential DNA methylation

    Schizophrenia is a highly heritable, neuropsychiatric disorder characterized by episodic psychosis and altered cognitive function. Despite success in identifying genetic variants associated with schizophrenia,...

    Eilis Hannon, Emma Dempster, Joana Viana, Joe Burrage, Adam R. Smith, Ruby Macdonald, David St Clair, Colette Mustard, Gerome Breen, Sebastian Therman, Jaakko Kaprio, Timothea Toulopoulou, Hilleke E. Hulshoff Pol, Marc M. Bohlken, Rene S. Kahn, Igor Nenadic…

    Genome Biology 2016 17:176

    Published on: 30 August 2016