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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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 |
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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 |
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