Evaluación de métodos de extracción de variantes en pruebas genómicas de patologías mitocondriales

Torralvo Márquez, María (2020). Evaluación de métodos de extracción de variantes en pruebas genómicas de patologías mitocondriales. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Evaluación de métodos de extracción de variantes en pruebas genómicas de patologías mitocondriales
Author/s:
  • Torralvo Márquez, María
Contributor/s:
  • Rodríguez Palenzuela, Pablo
  • Mínguez Paniagua, Pablo
Item Type: Final Project
Degree: Grado en Biotecnología
Date: July 2020
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

Rare diseases (RD) are those that affect less than 1 per 2,000 citizens (1). Up to date there are more than 6,000 RD described. Altogether, affect around 3.5% to 5.9% of the world population (2). Due to their individual low prevalence, the cohorts available for many of them are scarce, and the perceived need to invest in research still low. The consequence is a general lack of knowledge which makes harder to find the correct diagnosis and, therefore, getting the right treatment and family counselling to the families (3). A series of mitochondrial disorders are included inside the group of rare diseases. Symptoms are heterogeneous, and some of them are classified into specific syndromes, such as MELAS, LHON, KSS and syndromic forms of Retinitis Pigmentosa (4). Most of these diseases have a genetic cause, that may come from DNA variations in the nucleus and/or the mitochondrial. The development of Next Generation Sequencing (NGS) techniques has made an extreme impact on the diagnosis of genetic disorders, making easier and quicker producing DNA sequencing data covering big genomic regions at a lower price (5). Some aspects of the mitochondrial DNA and its inheritance pattern determine its sequencing and bioinformatics analysis. On one hand, there are multiple copies of mtDNA per mitochondrion and there are also many mitochondria in each cell, so mutations can be present at different frequencies (6), similarly to somatic variants in cancer tissues. Besides, mitochondrial variants have a non-Mendelian inheritance pattern. The main objective of this TFG is the development of a strategy for the detection of single nucleotide variants (SNV) and small insertions and deletions (Indel) in mtDNA of clinical samples. We have selected 4 variant callers previously used to analyze mtDNA: Mutetct2, a somatic variant caller from GATK (7); Varscan2 (8); LoFreq* (9) and Mutserve (10), being this the only one designed specifically for mitochondrial DNA sequencing data. We have tested the performances of the algorithms with simulated sequencing data and clinical samples. Based on both results, we have determined that the best approach is the combination of two programs, LoFreq to call SNVs and Mutserve for Indels. We implemented a protocol to use with the data produced by the sequencer that provides a final file with variants that can be further filtered and prioritized. It has been integrated within the reanalysis pipeline of the Genetics Department of IIS-Fundación Jiménez Díaz and will help with the correct diagnosis of patients suffering from mitochondrial rare diseases.

More information

Item ID: 66528
DC Identifier: http://oa.upm.es/66528/
OAI Identifier: oai:oa.upm.es:66528
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 25 Mar 2021 10:43
Last Modified: 25 Mar 2021 10:43
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