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Hutton M. Kearney

Other affiliations: Duke University
Bio: Hutton M. Kearney is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Medicine & Homologous recombination. The author has an hindex of 9, co-authored 12 publications receiving 1353 citations. Previous affiliations of Hutton M. Kearney include Duke University.

Papers
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Journal ArticleDOI
TL;DR: The American College of Medical Genetics has developed the following professional guidelines for the interpretation and reporting of copy number variation: evaluation of constitutional copy number variants detected in the postnatal setting.

751 citations

Journal ArticleDOI
TL;DR: To assist clinical laboratories in validation of microarray methodologies for constitutional applications, the American College of Medical Genetics and Genomics has produced the following revised professional standards and guidelines.

272 citations

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TL;DR: The detection of possible consanguinity by genomic testing and the factors confounding the inference of a specific p­arental relationship are described to guide the documentation of suspected consanguination by clinical laboratory professionals and to alert laboratories to the need to establish a reporting policy in conjunction with their ethics review committee and legal counsel.

139 citations

Journal ArticleDOI
TL;DR: The identity and function of the Drosophila melanogaster gene recombination defective (rec) is described and it is shown that REC encodes a member of the mini-chromosome maintenance (MCM) protein family, which is essential for DNA replication and found in all eukaryotes.
Abstract: Crossovers ensure the accurate segregation of homologous chromosomes from one another during meiosis. Here, we describe the identity and function of the Drosophila melanogaster gene recombination defective (rec), which is required for most meiotic crossing over. We show that rec encodes a member of the mini-chromosome maintenance (MCM) protein family. Six MCM proteins (MCM2–7) are essential for DNA replication and are found in all eukaryotes. REC is the Drosophila ortholog of the recently identified seventh member of this family, MCM8. Our phylogenetic analysis reveals the existence of yet another family member, MCM9, and shows that MCM8 and MCM9 arose early in eukaryotic evolution, though one or both have been lost in multiple eukaryotic lineages. Drosophila has lost MCM9 but retained MCM8, represented by REC. We used genetic and molecular methods to study the function of REC in meiotic recombination. Epistasis experiments suggest that REC acts after the Rad51 ortholog SPN-A but before the endonuclease MEI-9. Although crossovers are reduced by 95% in rec mutants, the frequency of noncrossover gene conversion is significantly increased. Interestingly, gene conversion tracts in rec mutants are about half the length of tracts in wild-type flies. To account for these phenotypes, we propose that REC facilitates repair synthesis during meiotic recombination. In the absence of REC, synthesis does not proceed far enough to allow formation of an intermediate that can give rise to crossovers, and recombination proceeds via synthesis-dependent strand annealing to generate only noncrossover products.

103 citations

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TL;DR: The American College of Medical Genetics, as the professional organization of board-certified clinical laboratory geneticists, outlines recommendations for the design and performance expectations for clinical genomic copy number microarrays and associated software intended for use in the postnatal setting for detection of constitutional abnormalities.

93 citations


Cited by
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Journal ArticleDOI
TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.

17,834 citations

Journal ArticleDOI
TL;DR: It is recommended that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here and encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected.

2,215 citations

Journal ArticleDOI
03 Jun 2015-Thyroid
TL;DR: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC and developed 67 evidence-based recommendations to assist clinicians in the care of Patients with MTC.
Abstract: Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendati...

1,504 citations

Journal ArticleDOI
TL;DR: 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B), to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor in all patients with advanced-stage adenocarcinoma.

1,230 citations

Journal ArticleDOI
TL;DR: An overview of recent biochemical and structural analyses of the Rad52 group proteins is provided and how this information can be incorporated into genetic studies of recombination is discussed.
Abstract: The process of homologous recombination is a major DNA repair pathway that operates on DNA double-strand breaks, and possibly other kinds of DNA lesions, to promote error-free repair. Central to the process of homologous recombination are the RAD52 group genes (RAD50, RAD51, RAD52, RAD54, RDH54/TID1, RAD55, RAD57, RAD59, MRE11, and XRS2), most of which were identified by their requirement for the repair of ionizing-radiation-induced DNA damage in Saccharomyces cerevisiae. The Rad52 group proteins are highly conserved among eukaryotes, and Rad51, Mre11, and Rad50 are also conserved in prokaryotes and archaea. Recent studies showing defects in homologous recombination and double-strand break repair in several human cancer-prone syndromes have emphasized the importance of this repair pathway in maintaining genome integrity. Although sensitivity to ionizing radiation is a universal feature of rad52 group mutants, the mutants show considerable heterogeneity in different assays for recombinational repair of double-strand breaks and spontaneous mitotic recombination. Herein, I provide an overview of recent biochemical and structural analyses of the Rad52 group proteins and discuss how this information can be incorporated into genetic studies of recombination.

1,012 citations