Artículo
Curating the gnomAD database: Report of novel variants in the globin‐coding genes and bioinformatics analysis
Scheps, Karen
; Hasenahuer, Marcia Anahí
; Parisi, Gustavo Daniel
; Targovnik, Hector Manuel
; Fornasari, María Elisa
Fecha de publicación:
25/09/2019
Editorial:
Wiley-liss, Div John Wiley & Sons Inc
Revista:
Human Mutation
ISSN:
1059-7794
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Massive parallel sequencing technologies are facilitating the faster identification of sequence variants with the consequent capability of untangling the molecular bases of many human genetic syndromes. However, it is not always easy to understand the impact of novel variants, especially for missense changes, which can lead to a spectrum of phenotypes. This study presents a custom‐designed multistep methodology to evaluate the impact of novel variants aggregated in the genome aggregation database for the HBB, HBA2, and HBA1 genes, by testing and improving its performance with a dataset of previously described alterations affecting those same genes. This approach scored high sensitivity and specificity values and showed an overall better performance than sequence‐derived predictors, highlighting the importance of protein conformation and interaction specific analyses in curating variant databases. This study also describes the strengths and limitations of these structural studies and allows identifying residues in the globin chains more prone to tolerate substitutions.
Palabras clave:
AHSP
,
FOLDX
,
GNOMAD
,
HEMOGLOBINOPATHIES
,
SEQUENCE VARIANTS
,
STRUCTURAL ANALYSES
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Articulos(INIGEM)
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Targovnik, Hector Manuel; Fornasari, María Elisa; Curating the gnomAD database: Report of novel variants in the globin‐coding genes and bioinformatics analysis; Wiley-liss, Div John Wiley & Sons Inc; Human Mutation; 41; 1; 25-9-2019; 81-102
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