ArticleAmerican journal of human genetics2014
Cryptic and complex chromosomal aberrations in early-onset neuropsychiatric disorders.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Review
- Impact and characterization of serial structural variations across humans and great apes.Nature communications · 2024Article
- A Balanced Translocation in Kallmann Syndrome Implicates a Long Noncoding RNA, RMST, as a GnRH Neuronal Regulator.The Journal of clinical endocrinology and metabolism · 2020Article
- Evaluating Structural Variation Detection Tools for Long-Read Sequencing Datasets inFrontiers in genetics · 2020Article
- Defining the Genetic, Genomic, Cellular, and Diagnostic Architectures of Psychiatric Disorders.Cell · 2019Review
- Translating genomics to the clinical diagnosis of disorders/differences of sex development.Current topics in developmental biology · 2019Review
- Complex structural variants in Mendelian disorders: identification and breakpoint resolution using short- and long-read genome sequencing.Genome medicine · 2018Article
- The role of genetics and genomics in clinical psychiatry.Dialogues in clinical neuroscience · 2018Review
- Phenotypic interpretation of complex chromosomal rearrangements informed by nucleotide-level resolution and structural organization of chromatin.European journal of human genetics : EJHG · 2018Article
- A recurrence-based approach for validating structural variation using long-read sequencing technology.GigaScience · 2017Article
- panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics.Human mutation · 2017Article
- Complex and Dynamic Chromosomal Rearrangements in a Family With Seemingly Non-Mendelian Inheritance of Dopa-Responsive Dystonia.JAMA neurology · 2017Article
- Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome.Genome biology · 2017Article
- Implication of LRRC4C and DPP6 in neurodevelopmental disorders.American journal of medical genetics. Part A · 2017Article
- The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.Nature genetics · 2017Article
- Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.Endocrine reviews · 2016Review
- Structural Chromosomal Rearrangements Require Nucleotide-Level Resolution: Lessons from Next-Generation Sequencing in Prenatal Diagnosis.American journal of human genetics · 2016Article
- Neuropsychiatric genomics in precision medicine: diagnostics, gene discovery, and translation.Dialogues in clinical neuroscience · 2016Review
- Explorations to improve the completeness of exome sequencing.BMC medical genomics · 2016Article
- Resolving complex structural genomic rearrangements using a randomized approach.Genome biology · 2016Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
Structural variation (SV) is a significant component of the genetic etiology of both neurodevelopmental and psychiatric disorders; however, routine guidelines for clinical genetic screening have been established only in the former category. Genome-wide chromosomal microarray (CMA) can detect genomic imbalances such as copy-number variants (CNVs), but balanced chromosomal abnormalities (BCAs) still require karyotyping for clinical detection. Moreover, submicroscopic BCAs and subarray threshold CNVs are intractable, or cryptic, to both CMA and karyotyping. Here, we performed whole-genome sequencing using large-insert jumping libraries to delineate both cytogenetically visible and cryptic SVs in a single test among 30 clinically referred youth representing a range of severe neuropsychiatric conditions. We detected 96 SVs per person on average that passed filtering criteria above our highest-confidence resolution (6,305 bp) and an additional 111 SVs per genome below this resolution. These SVs rearranged 3.8 Mb of genomic sequence and resulted in 42 putative loss-of-function (LoF) or gain-of-function mutations per person. We estimate that 80% of the LoF variants were cryptic to clinical CMA. We found myriad complex and cryptic rearrangements, including a "paired" duplication (360 kb, 169 kb) that flanks a 5.25 Mb inversion that appears in 7 additional cases from clinical CNV data among 47,562 individuals. Following convergent genomic profiling of these independent clinical CNV data, we interpreted three SVs to be of potential clinical significance. These data indicate that sequence-based delineation of the full SV mutational spectrum warrants exploration in youth referred for neuropsychiatric evaluation and clinical diagnostic SV screening more broadly.
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