Publications by authors named "Greg M Cooper"

Translational research has tended to ignore the question of whether receiving a genomic diagnosis provides utility in community care contexts outside of doctors' offices and hospitals. However, empirical research with parents has highlighted numerous ways that a genomic diagnosis might be of practical value in the care provided by teachers, physical or occupational therapists, speech-language pathologists, behavior analysts, and nonphysician mental health providers. In this essay, we propose a new conceptual model of genomic utility that offers the opportunity to better capture a broad range of potential implications of genomic technologies for families in various social and organizational systems.

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The desire of parents to obtain a genetic diagnosis for their child with intellectual disability and associated symptoms has long been framed as a diagnostic odyssey, an arduous and sometimes perilous journey focused on the goal of identifying a cause for the child's condition. Semi-structured interviews (N = 60) were conducted with parents of children (N = 59, aged 2-24 years) with intellectual disability and/or developmental delay (IDD) who underwent genome sequencing at a single pediatric multispecialty clinic. Interviews were conducted after parents received their child's sequencing result (positive findings, negative findings, or variants of unknown significance).

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Harmonization of variant pathogenicity classification across laboratories is important for advancing clinical genomics. The two CLIA-accredited Electronic Medical Record and Genomics Network sequencing centers and the six CLIA-accredited laboratories and one research laboratory performing genome or exome sequencing in the Clinical Sequencing Evidence-Generating Research Consortium collaborated to explore current sources of discordance in classification. Eight laboratories each submitted 20 classified variants in the ACMG secondary finding v.

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The originally published version of this Article contained errors in Fig. 2. The numbers below the black arrowheads were incorrect; please see incorrect Figure in associated Correction.

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Purpose: Clinical sequencing emerging in health care may result in secondary findings (SFs).

Methods: Seventy-four of 6240 (1.2%) participants who underwent genome or exome sequencing through the Clinical Sequencing Exploratory Research (CSER) Consortium received one or more SFs from the original American College of Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we assessed clinical and psychosocial actions.

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Purpose: Eliciting and understanding patient and research participant preferences regarding return of secondary test results are key aspects of genomic medicine. A valid instrument should be easily understood without extensive pretest counseling while still faithfully eliciting patients' preferences.

Methods: We conducted focus groups with 110 adults to understand patient perspectives on secondary genomic findings and the role that preferences should play.

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Article Synopsis
  • - Evaluating genetic variants for pathogenicity is complex due to the various types of evidence, leading to the need for standardized guidelines, which were established by ACMG and AMP in 2015.
  • - A pilot study involving nine molecular diagnostic labs tested these guidelines on 99 variants, showing high agreement within labs (79%) but low agreement across labs (34%) initially.
  • - After discussions and revisions of the ACMG-AMP criteria, the concordance across labs improved to 71%, highlighting the importance of collaborative review and clarity in standardizing variant interpretations for Mendelian diseases.
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Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults.

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Background: Bone morphogenetic protein 2 (BMP-2) has been used to reconstruct mandibular defects. An elegant addition to this reconstruction method would be incorporation of a nerve graft wrapped in a BMP-2 carrier to reconstitute the inferior alveolar nerve (IAN) and restore sensation to the lower face. We developed a rabbit model to determine the effect BMP-2 has on nerve regeneration following neurorrhaphy.

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Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. We hypothesize that individually rare structural variants contribute to the illness. Microdeletions and microduplications >100 kilobases were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia and 268 ancestry-matched controls.

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