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"Nagy, Gregory"
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DNA repair function scores for 2172 variants in the BRCA1 amino-terminus
Single nucleotide variants are the most frequent type of sequence changes detected in the genome and these are frequently variants of uncertain significance (VUS). VUS are changes in DNA for which disease risk association is unknown. Thus, methods that classify the functional impact of a VUS can be used as evidence for variant interpretation. In the case of the breast and ovarian cancer specific tumor suppressor protein, BRCA1, pathogenic missense variants frequently score as loss of function in an assay for homology-directed repair (HDR) of DNA double-strand breaks. We previously published functional results using a multiplexed assay for 1056 amino acid substitutions residues 2–192 in the amino terminus of BRCA1. In this study, we have re-assessed the data from this multiplexed assay using an improved analysis pipeline. These new analysis methods yield functional scores for more variants in the first 192 amino acids of BRCA1, plus we report new results for BRCA1 amino acid residues 193–302. We now present the functional classification of 2172 BRCA1 variants in BRCA1 residues 2–302 using the multiplexed HDR assay. Comparison of the functional determinations of the missense variants with clinically known benign or pathogenic variants indicated 93% sensitivity and 100% specificity for this assay. The results from BRCA1 variants tested in this assay are a resource for clinical geneticists for evidence to evaluate VUS in BRCA1 .
Journal Article
Gender and Genre in the Folklore of Middle India
A Choice Outstanding Academic Book for 1997 \"In this superbly crafted, absorbing book, Flueckiger explores the relationships among folklore genres in the Chattisgarh region of north India, achieving a pioneering model of the study of a 'folklore system' in its entirety. . . . This is ethnographic scholarship at its best. The multigenre approach is a major contribution, and this rich book should be read by all students of folklore, literature, performance, and South Asia.\"--Choice
eBook
Multiplexed assay of variant effect reveals residues of functional importance in the BRCA1 coiled-coil and serine cluster domains
Delineating functionally normal variants from functionally abnormal variants in tumor suppressor proteins is critical for cancer surveillance, prognosis, and treatment options. BRCA1 is a protein that has many variants of uncertain significance which are not yet classified as functionally normal or abnormal. In vitro functional assays can be used to identify the functional impact of a variant when the variant has not yet been categorized through clinical observation. Here we employ a homology-directed repair (HDR) reporter assay to evaluate over 300 missense and nonsense BRCA1 variants between amino acid residues 1280 and 1576, which encompasses the coiled-coil and serine cluster domains. Functionally abnormal variants tended to cluster in residues known to interact with PALB2, which is critical for homology-directed repair. Multiplexed results were confirmed by singleton assay and by ClinVar database variant interpretations. Comparison of multiplexed results to designated benign or likely benign or pathogenic or likely pathogenic variants in the ClinVar database yielded 100% specificity and 100% sensitivity of the multiplexed assay. Clinicians can reference the results of this functional assay for help in guiding cancer treatment and surveillance options. These results are the first to evaluate this domain of BRCA1 using a multiplexed approach and indicate the importance of this domain in the DNA repair process.
Journal Article
Greek Literature in the Classical Period: The Prose of Historiography and Oratory
This volume is available on its own or as part of the seven volume set, Greek Literature . This collection reprints in facsimile the most influential scholarship published in this field during the twentieth century. For a complete list of the volume titles in this set, see the listing for Greek Literature [ISBN 0-8153-3681-0]. A full table of contents can be obtained by email: reference@routledge-ny.com.
Gregory Nagy is Professor of Classics at Harvard University and Director of the Center for Hellenic Studies in Washington, D.C. He has written and edited numerous books on Greek literature, including Homeric Questions , The Everyman's Library The Iliad , Greek Mythology and Poetics , and Poetry as Performance .
eBook
Greek Literature in the Roman Period and in Late Antiquity
First published in 2002. Routledge is an imprint of Taylor & Francis, an informa company.
Gregory Nagy is Professor of Classics at Harvard University and Director of the Center for Hellenic Studies in Washington, D.C. He has written and edited numerous books on Greek literature, including Homeric Questions , The Everyman's Library The Iliad , Greek Mythology and Poetics , and Poetry as Performance .
eBook
Homeric Responses
The HomericIliadandOdysseyare among the world's foremost epics. Yet, millennia after their composition, basic questions remain about them. Who was Homer-a real or an ideal poet? When were the poems composed-at a single point in time, or over centuries of composition and performance? And how were the poems committed to writing? These uncertainties have been known as The Homeric Question, and many scholars, including Gregory Nagy, have sought to solve it.
InHomeric Responses,Nagy presents a series of essays that further elaborate his theories regarding the oral composition and evolution of the Homeric epics. Building on his previous work inHomeric QuestionsandPoetry as Performance: Homer and Beyondand responding to some of his critics, he examines such issues as the importance of performance and the interaction between audience and poet in shaping the poetry; the role of the rhapsode (the performer of the poems) in the composition and transmission of the poetry; the \"irreversible mistakes\" and cross-references in theIliadandOdysseyas evidences of artistic creativity; and the Iliadic description of the shield of Achilles as a pointer to the world outside the poem, the polis of the audience.
eBook