Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia

Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the la...

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Auteurs principaux:	Juliana Lago, Helena Groot, Diego Navas, Paula Lago, María Gamboa, Dayana Calderón, Diana C. Polanía-Villanueva
Format:	article
Langue:	EN
Publié:	MDPI AG 2021
Sujets:	hemophilia von Willebrand Disease (VWD) high-resolution melting (HRM) genetic diagnosis Python code denaturation domain Genetics QH426-470
Accès en ligne:	https://doaj.org/article/6e74fb95a19141018250ad4fe50abcaf
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spelling	oai:doaj.org-article:6e74fb95a19141018250ad4fe50abcaf2021-11-25T17:42:14ZGenetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia10.3390/genes121118072073-4425https://doaj.org/article/6e74fb95a19141018250ad4fe50abcaf2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1807https://doaj.org/toc/2073-4425Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the <i>F8, F9</i>, or the <i>VWF</i> gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.Juliana LagoHelena GrootDiego NavasPaula LagoMaría GamboaDayana CalderónDiana C. Polanía-VillanuevaMDPI AGarticlehemophiliavon Willebrand Disease (VWD)high-resolution melting (HRM)genetic diagnosisPython codedenaturation domainGeneticsQH426-470ENGenes, Vol 12, Iss 1807, p 1807 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hemophilia von Willebrand Disease (VWD) high-resolution melting (HRM) genetic diagnosis Python code denaturation domain Genetics QH426-470
spellingShingle	hemophilia von Willebrand Disease (VWD) high-resolution melting (HRM) genetic diagnosis Python code denaturation domain Genetics QH426-470 Juliana Lago Helena Groot Diego Navas Paula Lago María Gamboa Dayana Calderón Diana C. Polanía-Villanueva Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia
description	Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the <i>F8, F9</i>, or the <i>VWF</i> gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.
format	article
author	Juliana Lago Helena Groot Diego Navas Paula Lago María Gamboa Dayana Calderón Diana C. Polanía-Villanueva
author_facet	Juliana Lago Helena Groot Diego Navas Paula Lago María Gamboa Dayana Calderón Diana C. Polanía-Villanueva
author_sort	Juliana Lago
title	Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia
title_short	Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia
title_full	Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia
title_fullStr	Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia
title_full_unstemmed	Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia
title_sort	genetic and bioinformatic strategies to improve diagnosis in three inherited bleeding disorders in bogotá, colombia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e74fb95a19141018250ad4fe50abcaf
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Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia

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