OMIA 002342-9940 : Ciliary dyskinesia, primary, CCDC65-related in Ovis aries

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 615504 (trait) , 611088 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2022

Cross-species summary: This phene was initially named 'Haplotype with homozygous deficiency, LDHH6' and was renamed after identification of the causal gene and characterisation of the disease. [29/1/2022]

Species-specific name: Haplotype with homozygous deficiency, LDHH6

Species-specific description: Ben Braiek et al. (2021): “By scanning the genome of 19,102 Lacaune sheep using 50 k single nucleotide polymorphism (SNP) phased genotypes and pedigree data, we identified 11 Lacaune deficient homozygous haplotypes (LDHH1 to LDHH11) showing a highly significant deficit of homozygous animals ranging from 79 to 100%. These haplotypes located on chromosomes 3, 4, 13, 17 and 18, spanned regions from 1.2 to 3.0 Mb long with a frequency of heterozygous carriers between 3.7 and 12.1%. When we compared at-risk matings (between carrier rams and daughters of carrier rams) and safe matings, seven of the 11 haplotypes were associated with a significant alteration of two fertility traits, a reduced success of artificial insemination (LDHH1, 2, 8 and 9), and/or an increased stillbirth rate (LDHH3, 6, 8, 9, and 10). The 11 haplotypes were also tested for a putative selective advantage of heterozygous carrier rams based on their daughter yield deviation for six dairy traits (milk, fat and protein yields, fat and protein contents and lactation somatic cell score). LDHH1, 3, 4, 5, 7, 9 and 11 were associated with positive effects on at least one selected dairy trait, in particular milk yield.”

Inheritance: Ben Braiek et al. (2022) "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".

Mapping: Position on ovine genome assembly Oar_v3.1: LDHH6 OAR3: 136.2–137.4 Mb

Molecular basis: Ben Braiek et al. (2022) "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".

Clinical features: Ben Braiek et al. (2022): "CCDC65 is involved in the assembly of the nexin-dynein regulatory complex for the formation of microtubules in ciliated cells. . . . 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."

Prevalence: Ben Braiek et al. (2022) reported that the frequency of the c.521T variant in 2,952 French Lacaune Dairy lambs was 7%. They also reported that the "LDHH6 heterozygous carrier frequency observed [in male French Lacaune Dairy lambs considered for genomic selection] is stable in the population between 2017 and 2021" at around 12%. However, the frequency differs substantially between two breeding companies: around 16% in one company and around 6% in the other.

Also, Ben Braiek et al. (2022) reported "the segregation of the CCDC65 c.521G > T variant not only in the Lacaune dairy population but also in the Lacaune meat and Blanche du Massif Central (BMC) populations".

Genetic testing: Ben Braiek et al. (2022): "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%."

Breeds: Blanche du Massif Central, Lacaune.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CCDC65 coiled-coil domain containing 65 Ovis aries 3 NC_056056.1 (137300335..137291505) CCDC65 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1403 Blanche du Massif Central Lacaune Ciliary dyskinesia, primary (respiratory failure) CCDC65 LDHH6 nonsense (stop-gain) Naturally occurring variant Oar_rambouillet_v1.0 3 g.147207999C>A c.521G>T p.(E111*) XM_004006389.4; XP_004006438.1; published as NC_040254.1:g.147,207,999C>A rs1085624756 2021 35052387

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2021 Ben Braiek, M., Fabre, S., Hozé, C., Astruc, J.M., Moreno-Romieux, C. :
Identification of homozygous haplotypes carrying putative recessive lethal mutations that compromise fertility traits in French Lacaune dairy sheep. Genet Sel Evol 53:41, 2021. Pubmed reference: 33932977. DOI: 10.1186/s12711-021-00634-1.
Ben Braiek, M., Moreno-Romieux, C., Allain, C., Bardou, P., Bordes, A., Debat, F., Drögemüller, C., Plisson-Petit, F., Portes, D., Sarry, J., Tadi, N., Woloszyn, F., Fabre, S. :
A Nonsense Variant in <i>CCDC65</i> Gene Causes Respiratory Failure Associated with Increased Lamb Mortality in French Lacaune Dairy Sheep. Genes (Basel) 13:45, 2021. Pubmed reference: 35052387. DOI: 10.3390/genes13010045.

Edit History


  • Created by Imke Tammen2 on 26 May 2021
  • Changed by Imke Tammen2 on 26 May 2021
  • Changed by Frank Nicholas on 05 Jan 2022
  • Changed by Imke Tammen2 on 29 Jan 2022