A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep

Braiek, Ben; 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 (2021). A Nonsense Variant in CCDC65 Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep. Genes, 13(1), p. 45. MDPI 10.3390/genes13010045

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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%.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Drögemüller, Cord

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

27 Dec 2021 14:26

Last Modified:

07 Aug 2024 15:45

Publisher DOI:

10.3390/genes13010045

BORIS DOI:

10.48350/163168

URI:

https://boris.unibe.ch/id/eprint/163168

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