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

Autor: Hisey EA; Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Hermans H; Department of Clinical Sciences, Utrecht University, Yalelaan 112-114, NL-3584, CM, Utrecht, The Netherlands., Lounsberry ZT; Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Avila F; Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Grahn RA; Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA., Knickelbein KE; Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.; Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA, USA., Duward-Akhurst SA; Department of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN, USA., McCue ME; Department of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN, USA., Kalbfleisch TS; Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA., Lassaline ME; Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA., Back W; Department of Clinical Sciences, Utrecht University, Yalelaan 112-114, NL-3584, CM, Utrecht, The Netherlands.; Department of Surgery and Anaesthesia of Domestic Animals, Ghent University, Merelbeke, Belgium., Bellone RR; Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA. rbellone@ucdavis.edu.; Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA. rbellone@ucdavis.edu.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2020 Nov 30; Vol. 21 (1), pp. 848. Date of Electronic Publication: 2020 Nov 30.
DOI: 10.1186/s12864-020-07265-8
Abstrakt: 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 (p corrected  = 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: MEDLINE
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