MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples

Acta Neuropathologica Communications
Marco SavareseVincenzo Nigro

Abstract

Mutations in ~100 genes cause muscle diseases with complex and often unexplained genotype/phenotype correlations. Next-generation sequencing studies identify a greater-than-expected number of genetic variations in the human genome. This suggests that existing clinical monogenic testing systematically miss very relevant information.We have created a core panel of genes that cause all known forms of nonsyndromic muscle disorders (MotorPlex). It comprises 93 loci, among which are the largest and most complex human genes, such as TTN, RYR1, NEB and DMD. MotorPlex captures at least 99.2% of 2,544 exons with a very accurate and uniform coverage. This quality is highlighted by the discovery of 20-30% more variations in comparison with whole exome sequencing. The coverage homogeneity has also made feasible to apply a cost-effective pooled sequencing strategy while maintaining optimal sensitivity and specificity.We studied 177 unresolved cases of myopathies for which the best candidate genes were previously excluded. We have identified known pathogenic variants in 52 patients and potential causative ones in further 56 patients. We have also discovered 23 patients showing multiple true disease-associated variants suggesting complex inher...Continue Reading

References

Dec 3, 2015·Neuromuscular Disorders : NMD·Anni EviläPeter Hackman
Apr 15, 2015·Neuromuscular Disorders : NMD·Ha Young ShinYoung-Chul Choi
Mar 28, 2016·Neuromuscular Disorders : NMD·Marco SavareseVincenzo Nigro
May 30, 2015·Revue neurologique·S GorokhovaM Krahn
Sep 16, 2016·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Audrone JakaitieneMario Rosario Guarracino
Mar 9, 2017·European Journal of Human Genetics : EJHG·Francesco TestaSandro Banfi
Jan 23, 2016·Muscle & Nerve·Corrado AngeliniVincenzo Nigro
Apr 23, 2015·European Journal of Human Genetics : EJHG·Giuseppina Di FruscioVincenzo Nigro
Sep 2, 2015·Journal of Neuromuscular Diseases·Valérie Biancalana, Jocelyn Laporte
Sep 14, 2019·Neurology. Genetics·Anna RubegniD Cassandrini
Jul 28, 2016·Current Opinion in Neurology·Vincenzo Nigro, Marco Savarese
Feb 15, 2020·Journal of Medical Genetics·Lois GardnerPhilip M Hopkins
Mar 21, 2020·Frontiers in Genetics·Marcella NeriAlessandra Ferlini
Sep 3, 2019·Molecular Genetics & Genomic Medicine·Jihye ParkDae-Hyun Jang
Jul 9, 2016·Orphanet Journal of Rare Diseases·C FiorilloItalian Network on Congenital Myopathies
Apr 12, 2016·Neurology. Genetics·Marina FaninCorrado Angelini
Nov 18, 2016·Journal of Neuromuscular Diseases·Jaya PunethaEric P Hoffman
Nov 18, 2016·Journal of Neuromuscular Diseases·Marco SavaresePeter Hackman
Feb 13, 2018·JAMA Neurology·Marco SavareseVincenzo Nigro
Aug 12, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Marco SavareseBjarne Udd
Feb 11, 2020·Journal of Neuromuscular Diseases·Marco SavareseBjarne Udd

Citations

Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
May 20, 2009·Bioinformatics·Heng Li, Richard M Durbin
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Dec 10, 2009·Nature Reviews. Genetics·Michael L Metzker
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Aug 3, 2010·Nature Methods·Jana Marie SchwarzDominik Seelow
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Aug 10, 2011·Current Opinion in Neurology·Vincenzo NigroGiulio Piluso
Nov 29, 2011·Nucleic Acids Research·Kim D PruittDonna R Maglott
Jan 20, 2012·European Journal of Human Genetics : EJHG·Christian GilissenJoris A Veltman
Feb 16, 2012·Annals of Neurology·Matthew B HarmsRobert H Baloh
Mar 2, 2012·Clinical Genetics·A N Desai, A Jere
Apr 4, 2012·Critical Reviews in Clinical Laboratory Sciences·Nigel G Laing
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Apr 25, 2012·Acta Neuropathologica·Nasim VasliJocelyn Laporte
Jan 5, 2013·Brain : a Journal of Neurology·Sebahattin CirakFrancesco Muntoni
Jan 15, 2013·Current Protocols in Human Genetics·Ivan AdzhubeiShamil R Sunyaev
Mar 8, 2013·Lancet·Eugenio Mercuri, Francesco Muntoni
Mar 13, 2013·Nature Reviews. Genetics·Heidi L Rehm
Jul 28, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Heidi L RehmWorking Group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Commitee
Aug 14, 2013·Annals of Neurology·Doris G Leung, Kathryn R Wagner
Oct 1, 2013·American Journal of Human Genetics·Sabrina SacconiSilvère M van der Maarel
Oct 4, 2013·The New England Journal of Medicine·Yaping YangChristine M Eng
Dec 19, 2013·Cancer Metastasis Reviews·Francesco CreaCheryl D Helgason
Jan 22, 2014·Neuromuscular Disorders : NMD·Jean-Claude Kaplan, Dalil Hamroun
Jun 7, 2014·American Journal of Human Genetics·Chandree L BeaulieuKym M Boycott

Related Concepts

In Silico
Exons
Myopathic Carnitine Deficiency
Pathogenic Organism
Candidate Disease Gene
Myopathy
RYR1
Soleus Muscle Structure
Whole Exome Sequencing
Genetic Inheritance

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.