Biphasic survival analysis of trypanotolerance QTL in mice

Koudandé, O.D.; Thomson, Peter; Bovenhuis, H.; Iraqi, Fuad A.; Gibson, John P.; Arendonk, J.A.M. van

doi:10.1038/sj.hdy.6801096

Cited by 3 publications

(4 citation statements)

References 16 publications

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“…Identifying QTL act at different time points during challenge i.e. early v.s late phase was reported, earlier with trypanosome infection [ 28 ]. This is not surprising machines knowing that the host innate and adaptive immunity systems act at different time points during infection.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility to klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points

et al. 2014

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BackgroundKlebsiella pneumoniae (Kp) is a bacterium causing severe pneumonia in immunocompromised hosts and is often associated with sepsis. With the rise of antibiotic resistant bacteria, there is a need for new effective and affordable control methods; understanding the genetic architecture of susceptibility to Kp will help in their development. We performed the first quantitative trait locus (QTL) mapping study of host susceptibility to Kp infection in immunocompetent Collaborative Cross mice (CC). We challenged 328 mice from 73 CC lines intraperitoneally with 104 colony forming units of Kp strain K2. Survival and body weight were monitored for 15 days post challenge. 48 of the CC lines were genotyped with 170,000 SNPs, with which we mapped QTLs.ResultsCC lines differed significantly (P < 0.05) in mean survival time, between 1 to 15 days post infection, and broad sense heritability was 0.45. Distinct QTL were mapped at specific time points during the challenge. A QTL on chromosome 4 was found only on day 2 post infection, and QTL on chromosomes 8 and 18, only on day 8. By using the sequence variations of the eight inbred strain founders of the CC to refine QTL localization we identify several candidate genes.ConclusionHost susceptibility to Kp is a complex trait, controlled by multiple genetic factors that act sequentially during the course of infection.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-865) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Susceptibility to klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points

et al. 2014

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“…resistance to trypanosomosis in mice, Koudandé et al 2008). However, these QTLs are only suggestive and might not be confirmed.…”

Section: Lg1mentioning

confidence: 96%

“…It is not unexpected to find phase-specific QTLs, as mechanisms of disease resistance can be biphasic or even multiphasic (e.g. resistance to trypanosomosis in mice, Koudandé et al 2008). A first line of Table 3 Oxford plot comparing the sea bream linkage and RH map.…”

Section: Lg11mentioning

confidence: 99%

Quantitative trait loci for resistance to fish pasteurellosis in gilthead sea bream (Sparus aurata)

et al. 2010

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Fish pasteurellosis is a bacterial disease causing important losses in farmed fish, including gilthead sea bream, a teleost fish of great relevance in marine aquaculture. We report in this study a QTL analysis for resistance to fish pasteurellosis in this species. An experimental population of 500 offspring originating from eight sires and six dams in a single mass-spawning event was subjected to a disease challenge with Photobacterium damselae subsp. piscicida (Phdp), the causative agent of fish pasteurellosis. A total of 151 microsatellite loci were genotyped in the experimental population, and half-sib regression QTL analysis was carried out on two continuous traits, body length at time of death and survival, and for two binary traits, survival at day 7 and survival at day 15, when the highest peaks of mortality were observed. Two significant QTLs were detected for disease resistance. The first one was located on linkage group LG3 affecting late survival (survival at day 15). The second one, for overall survival, was located on LG21, which allowed us to highlight a potential marker (Id13) linked to disease resistance. A significant QTL was also found for body length at death on LG6 explaining 5-8% of the phenotypic variation.

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“…A study by Koudande et al . [ 63 ] used marker-associated introgression to transfer trypanotolerance QTLs from a donor mouse strain into a recipient mouse strain. The study showed that the introgressed mice had improved survival time to challenge than the recipient mice.…”

Section: Trypanotolerance In Livestockmentioning

confidence: 99%

Breeding of African sheep reared under low-input/output smallholder production systems for trypanotolerance

Malatji

2022

Vet World

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Trypanosomiasis is a disease caused by unicellular protozoan parasites. Small ruminants succumb to trypanosomiasis in areas of high tsetse fly challenge, resulting in serious economic loss often to farmers in low-input smallholder systems. At present, trypanosomiasis is treated with trypanocidal drugs, but access to these can be limited, and increasing parasite resistance raises questions about their efficacy. The development of trypanotolerance in small ruminant flocks through targeted breeding strategies is considered a sustainable and economical option for controlling African trypanosomiasis. Recently, quantitative trait loci (QTLs) associated with trypanotolerance traits in sheep have been reported. The results of these studies form the basis for more studies to identify QTLs associated with trypanosomiasis resistance, particularly in African livestock species. For example, signatures of positive selection for trypanotolerance have been identified using genome-wide single-nucleotide polymorphism data. However, there are several challenges in performing genetic analyses using data from low-input smallholder systems, including a lack of recorded pedigree and production records and the need for large sample sizes when flock sizes are often fewer than 50 animals. Breeding strategies to improve trypanotolerance should also preserve existing genetic diversity as well as minimize excessive genetic introgression by trypanosusceptible breeds. This review discusses the possibilities of breeding for trypanosome tolerance/resistance in low-input/low-output small ruminant production systems. Potential challenges are outlined, and potential available genetic resources are described as a foundation for future work.

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Biphasic survival analysis of trypanotolerance QTL in mice

Cited by 3 publications

References 16 publications

Susceptibility to klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points

Susceptibility to klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points

Quantitative trait loci for resistance to fish pasteurellosis in gilthead sea bream (Sparus aurata)

Breeding of African sheep reared under low-input/output smallholder production systems for trypanotolerance

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