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A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep
We recently demonstrated that the Lacaune deficient homozygous haplotype 6 (LDHH6) potentially hosts a recessive perinatal lethal mutation in Lacaune dairy sheep mapped on OAR3. In the present study, we have analyzed the whole-genome sequences of two Lacaune ram heterozygous carriers of LDHH6. After...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774411/ https://www.ncbi.nlm.nih.gov/pubmed/35052387 http://dx.doi.org/10.3390/genes13010045 |
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author | Ben Braiek, Maxime Moreno-Romieux, Carole Allain, Charlotte Bardou, Philippe Bordes, Arnaud Debat, Frédéric Drögemüller, Cord Plisson-Petit, Florence Portes, David Sarry, Julien Tadi, Némuel Woloszyn, Florent Fabre, Stéphane |
author_facet | Ben Braiek, Maxime Moreno-Romieux, Carole Allain, Charlotte Bardou, Philippe Bordes, Arnaud Debat, Frédéric Drögemüller, Cord Plisson-Petit, Florence Portes, David Sarry, Julien Tadi, Némuel Woloszyn, Florent Fabre, Stéphane |
author_sort | Ben Braiek, Maxime |
collection | PubMed |
description | We recently demonstrated that the Lacaune deficient homozygous haplotype 6 (LDHH6) potentially hosts a recessive perinatal lethal mutation in Lacaune dairy sheep mapped on OAR3. In the present study, we have analyzed the whole-genome sequences of two Lacaune ram heterozygous carriers of LDHH6. After variant calling and filtering against the variants of 86 non-carrier rams, we have identified a single nucleotide variant (SNV) in the two LDHH6 carriers whose variant allele induced a premature stop codon (p.Glu111*) in the Coiled-Coil Domain Containing 65 (CCDC65) gene. CCDC65 is involved in the assembly of the nexin-dynein regulatory complex for the formation of microtubules in ciliated cells. In order to identify the phenotype in homozygous sheep, we generated at-risk matings (n = 17) between rams and ewes heterozygous for the candidate variant in CCDC65. A total of 16 lambs were born alive with five genotyped as homozygous carriers. The homozygous lambs suffered from respiratory problems, and four of them died within the first month of life. At necropsy, we observed a broad hepatization of lung lobes possibly induced by infectious pneumonia. The management of this lethal recessive allele (frequency of 0.06) through reasoned mating in the Lacaune sheep selection schemes could reduce lamb mortality by 2%. |
format | Online Article Text |
id | pubmed-8774411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87744112022-01-21 A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep Ben Braiek, Maxime Moreno-Romieux, Carole Allain, Charlotte Bardou, Philippe Bordes, Arnaud Debat, Frédéric Drögemüller, Cord Plisson-Petit, Florence Portes, David Sarry, Julien Tadi, Némuel Woloszyn, Florent Fabre, Stéphane Genes (Basel) Article We recently demonstrated that the Lacaune deficient homozygous haplotype 6 (LDHH6) potentially hosts a recessive perinatal lethal mutation in Lacaune dairy sheep mapped on OAR3. In the present study, we have analyzed the whole-genome sequences of two Lacaune ram heterozygous carriers of LDHH6. After variant calling and filtering against the variants of 86 non-carrier rams, we have identified a single nucleotide variant (SNV) in the two LDHH6 carriers whose variant allele induced a premature stop codon (p.Glu111*) in the Coiled-Coil Domain Containing 65 (CCDC65) gene. CCDC65 is involved in the assembly of the nexin-dynein regulatory complex for the formation of microtubules in ciliated cells. In order to identify the phenotype in homozygous sheep, we generated at-risk matings (n = 17) between rams and ewes heterozygous for the candidate variant in CCDC65. A total of 16 lambs were born alive with five genotyped as homozygous carriers. The homozygous lambs suffered from respiratory problems, and four of them died within the first month of life. At necropsy, we observed a broad hepatization of lung lobes possibly induced by infectious pneumonia. The management of this lethal recessive allele (frequency of 0.06) through reasoned mating in the Lacaune sheep selection schemes could reduce lamb mortality by 2%. MDPI 2021-12-24 /pmc/articles/PMC8774411/ /pubmed/35052387 http://dx.doi.org/10.3390/genes13010045 Text en © 2021 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 Ben Braiek, Maxime Moreno-Romieux, Carole Allain, Charlotte Bardou, Philippe Bordes, Arnaud Debat, Frédéric Drögemüller, Cord Plisson-Petit, Florence Portes, David Sarry, Julien Tadi, Némuel Woloszyn, Florent Fabre, Stéphane A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep |
title | A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep |
title_full | A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep |
title_fullStr | A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep |
title_full_unstemmed | A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep |
title_short | A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep |
title_sort | nonsense variant in ccdc65 gene causes respiratory failure associated with increased lamb mortality in french lacaune dairy sheep |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774411/ https://www.ncbi.nlm.nih.gov/pubmed/35052387 http://dx.doi.org/10.3390/genes13010045 |
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