Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses

Autor: Hisey, E. A., Hermans, H., Lounsberry, Z. T., Avila, F., Grahn, R. A., Knickelbein, K. E., Duward-Akhurst, S. A., McCue, M. E., Kalbfleisch, T. S., Lassaline, M. E., Back, W., Bellone, R. R., Heelkunde, dES AVR, CS_Welfare & emerging diseases
Přispěvatelé: Heelkunde, dES AVR, CS_Welfare & emerging diseases
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Distichiasis
Functional annotation of animal genomes
Genome-wide association study
Medical and Health Sciences
0403 veterinary science
Haplotype
2.1 Biological and endogenous factors
Aetiology
Genetics
0303 health sciences
04 agricultural and veterinary sciences
Biological Sciences
Functional annotation of animal genomes (FAANG)
Penetrance
Eyelash
Phenotype
symbols
Eyelid Diseases
Meibomian gland
Biotechnology
Research Article
lcsh:QH426-470
040301 veterinary sciences
Bioinformatics
Secondary infection
lcsh:Biotechnology
Locus (genetics)
Biology
03 medical and health sciences
symbols.namesake
lcsh:TP248.13-248.65
Information and Computing Sciences
Animals
Horses
Genotyping
Eye Disease and Disorders of Vision
030304 developmental biology
Whole Genome Sequencing
Histone marks
Human Genome
Eyelids
Whole genome sequencing (WGS)
Genome wide association study (GWAS)
lcsh:Genetics
Haplotypes
Mendelian inheritance
Horse Diseases
Genome wide association study
Genome-Wide Association Study
Zdroj: BMC Genomics, 21(1). BioMed Central
BMC genomics, vol 21, iss 1
BMC Genomics, Vol 21, Iss 1, Pp 1-13 (2020)
BMC Genomics
ISSN: 1471-2164
Popis: Background Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait. Results A genome wide association study (GWAS) was performed using the Axiom 670 k Equine Genotyping array (MNEc670k) utilizing 14 cases and 38 controls phenotyped for distichiasis. An additive single locus mixed linear model (EMMAX) approach identified a 1.83 Mb locus on ECA5 and a 1.34 Mb locus on ECA13 that reached genome-wide significance (pcorrected = 0.016 and 0.032, respectively). Only the locus on ECA13 withstood replication testing (p = 1.6 × 10− 5, cases: n = 5 and controls: n = 37). A 371 kb run of homozygosity (ROH) on ECA13 was found in 13 of the 14 cases, providing evidence for a recessive mode of inheritance. Haplotype analysis (hapQTL) narrowed the region of association on ECA13 to 163 kb. Whole-genome sequencing data from 3 cases and 2 controls identified a 16 kb deletion within the ECA13 associated haplotype (ECA13:g.178714_195130del). Functional annotation data supports a tissue-specific regulatory role of this locus. This deletion was associated with distichiasis, as 18 of the 19 cases were homozygous (p = 4.8 × 10− 13). Genotyping the deletion in 955 horses from 54 different breeds identified the deletion in only 11 non-Friesians, all of which were carriers, suggesting that this could be causal for this Friesian disorder. Conclusions This study identified a 16 kb deletion on ECA13 in an intergenic region that was associated with distichiasis in Friesian horses. Further functional analysis in relevant tissues from cases and controls will help to clarify the precise role of this deletion in normal and abnormal eyelash development and investigate the hypothesis of incomplete penetrance.
Databáze: OpenAIRE
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