Cargando…

Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model

Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal reg...

Descripción completa

Detalles Bibliográficos
Autores principales: Hernández-Goenaga, Juan, López-Abán, Julio, Blanco-Gómez, Adrián, Vicente, Belén, Burguillo, Francisco Javier, Pérez-Losada, Jesús, Muro, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573152/
https://www.ncbi.nlm.nih.gov/pubmed/37834216
http://dx.doi.org/10.3390/ijms241914768
_version_ 1785120395640176640
author Hernández-Goenaga, Juan
López-Abán, Julio
Blanco-Gómez, Adrián
Vicente, Belén
Burguillo, Francisco Javier
Pérez-Losada, Jesús
Muro, Antonio
author_facet Hernández-Goenaga, Juan
López-Abán, Julio
Blanco-Gómez, Adrián
Vicente, Belén
Burguillo, Francisco Javier
Pérez-Losada, Jesús
Muro, Antonio
author_sort Hernández-Goenaga, Juan
collection PubMed
description Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions involved, a backcross strategy was employed to generate high variation in schistosomiasis susceptibility. This strategy involved crossing the resistant C57BL/6J mouse strain with the susceptible CBA/2J strain. The resulting F1 females (C57BL/6J × CBA/2J) were then backcrossed with CBA/2J males to generate the backcross (BX) cohort. The BX mice exhibited a range of phenotypes, with disease severity varying from mild to severe disease, lacking a fully resistant group. We observed four levels of infection intensity using cluster and principal component analyses and K-means based on parasitological, pathological, and immunological trait measurements. The mice were genotyped with 961 informative SNPs, leading to the identification of 19 new quantitative trait loci (QTL) associated with parasite burden, liver lesions, white blood cell populations, and antibody responses. Two QTLs located on chromosomes 15 and 18 were linked to the number of granulomas, liver lesions, and IgM levels. The corresponding syntenic human regions are located in chromosomes 8 and 18. None of the significant QTLs had been reported previously.
format Online
Article
Text
id pubmed-10573152
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105731522023-10-14 Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model Hernández-Goenaga, Juan López-Abán, Julio Blanco-Gómez, Adrián Vicente, Belén Burguillo, Francisco Javier Pérez-Losada, Jesús Muro, Antonio Int J Mol Sci Article Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions involved, a backcross strategy was employed to generate high variation in schistosomiasis susceptibility. This strategy involved crossing the resistant C57BL/6J mouse strain with the susceptible CBA/2J strain. The resulting F1 females (C57BL/6J × CBA/2J) were then backcrossed with CBA/2J males to generate the backcross (BX) cohort. The BX mice exhibited a range of phenotypes, with disease severity varying from mild to severe disease, lacking a fully resistant group. We observed four levels of infection intensity using cluster and principal component analyses and K-means based on parasitological, pathological, and immunological trait measurements. The mice were genotyped with 961 informative SNPs, leading to the identification of 19 new quantitative trait loci (QTL) associated with parasite burden, liver lesions, white blood cell populations, and antibody responses. Two QTLs located on chromosomes 15 and 18 were linked to the number of granulomas, liver lesions, and IgM levels. The corresponding syntenic human regions are located in chromosomes 8 and 18. None of the significant QTLs had been reported previously. MDPI 2023-09-30 /pmc/articles/PMC10573152/ /pubmed/37834216 http://dx.doi.org/10.3390/ijms241914768 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hernández-Goenaga, Juan
López-Abán, Julio
Blanco-Gómez, Adrián
Vicente, Belén
Burguillo, Francisco Javier
Pérez-Losada, Jesús
Muro, Antonio
Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model
title Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model
title_full Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model
title_fullStr Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model
title_full_unstemmed Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model
title_short Identification of Genomic Regions Implicated in Susceptibility to Schistosoma mansoni Infection in a Murine Backcross Genetic Model
title_sort identification of genomic regions implicated in susceptibility to schistosoma mansoni infection in a murine backcross genetic model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573152/
https://www.ncbi.nlm.nih.gov/pubmed/37834216
http://dx.doi.org/10.3390/ijms241914768
work_keys_str_mv AT hernandezgoenagajuan identificationofgenomicregionsimplicatedinsusceptibilitytoschistosomamansoniinfectioninamurinebackcrossgeneticmodel
AT lopezabanjulio identificationofgenomicregionsimplicatedinsusceptibilitytoschistosomamansoniinfectioninamurinebackcrossgeneticmodel
AT blancogomezadrian identificationofgenomicregionsimplicatedinsusceptibilitytoschistosomamansoniinfectioninamurinebackcrossgeneticmodel
AT vicentebelen identificationofgenomicregionsimplicatedinsusceptibilitytoschistosomamansoniinfectioninamurinebackcrossgeneticmodel
AT burguillofranciscojavier identificationofgenomicregionsimplicatedinsusceptibilitytoschistosomamansoniinfectioninamurinebackcrossgeneticmodel
AT perezlosadajesus identificationofgenomicregionsimplicatedinsusceptibilitytoschistosomamansoniinfectioninamurinebackcrossgeneticmodel
AT muroantonio identificationofgenomicregionsimplicatedinsusceptibilitytoschistosomamansoniinfectioninamurinebackcrossgeneticmodel