Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.

In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal's health, productiv...

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Autores principales:	Michael P Heaton, Theodore S Kalbfleisch, Dustin T Petrik, Barry Simpson, James W Kijas, Michael L Clawson, Carol G Chitko-McKown, Gregory P Harhay, Kreg A Leymaster, International Sheep Genomics Consortium
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d621bf3cbf3d4ae58c392978b1e47d3f
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spelling	oai:doaj.org-article:d621bf3cbf3d4ae58c392978b1e47d3f2021-11-18T07:58:04ZGenetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.1932-620310.1371/journal.pone.0055490https://doaj.org/article/d621bf3cbf3d4ae58c392978b1e47d3f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23408992/?tool=EBIhttps://doaj.org/toc/1932-6203In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal's health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization-time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.Michael P HeatonTheodore S KalbfleischDustin T PetrikBarry SimpsonJames W KijasMichael L ClawsonCarol G Chitko-McKownGregory P HarhayKreg A LeymasterInternational Sheep Genomics ConsortiumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55490 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael P Heaton Theodore S Kalbfleisch Dustin T Petrik Barry Simpson James W Kijas Michael L Clawson Carol G Chitko-McKown Gregory P Harhay Kreg A Leymaster International Sheep Genomics Consortium Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.
description	In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal's health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization-time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.
format	article
author	Michael P Heaton Theodore S Kalbfleisch Dustin T Petrik Barry Simpson James W Kijas Michael L Clawson Carol G Chitko-McKown Gregory P Harhay Kreg A Leymaster International Sheep Genomics Consortium
author_facet	Michael P Heaton Theodore S Kalbfleisch Dustin T Petrik Barry Simpson James W Kijas Michael L Clawson Carol G Chitko-McKown Gregory P Harhay Kreg A Leymaster International Sheep Genomics Consortium
author_sort	Michael P Heaton
title	Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.
title_short	Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.
title_full	Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.
title_fullStr	Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.
title_full_unstemmed	Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.
title_sort	genetic testing for tmem154 mutations associated with lentivirus susceptibility in sheep.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d621bf3cbf3d4ae58c392978b1e47d3f
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Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.

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