A novel point mutation within the EDA gene causes an exon dropping in mature RNA in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal dysplasia

Gargani, Maria; Valentini, Alessio; Pariset, Lorraine

doi:10.1186/1746-6148-7-35

Cited by 12 publications

(15 citation statements)

References 23 publications

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“…Studies reported a QTL in the PAPD7 , ICE1 , and LOC101907249 gene regions associated with percentage abnormal sperm in Holstein bulls [ 34 ] and calving ease in Angus breed cows [ 33 ]. The EDARADD gene participates in cell differentiation and mutations in this gene can result in abnormal development of tissues and organs of ectodermal origin [ 35 ]. In this region, a QTL associated with pregnancy rate trait have been reported by Boichard et al [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Candidate genes for male and female reproductive traits in Canchim beef cattle

Buzanskas

Grossi²,

Ventura

et al. 2017

J Animal Sci Biotechnol

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BackgroundBeef cattle breeding programs in Brazil have placed greater emphasis on the genomic study of reproductive traits of males and females due to their economic importance. In this study, genome-wide associations were assessed for scrotal circumference at 210 d of age, scrotal circumference at 420 d of age, age at first calving, and age at second calving, in Canchim beef cattle. Data quality control was conducted resulting in 672,778 SNPs and 392 animals.ResultsAssociated SNPs were observed for scrotal circumference at 420 d of age (435 SNPs), followed by scrotal circumference at 210 d of age (12 SNPs), age at first calving (six SNPs), and age at second calving (four SNPs). We investigated whether significant SNPs were within genic or surrounding regions. Biological processes of genes were associated with immune system, multicellular organismal process, response to stimulus, apoptotic process, cellular component organization or biogenesis, biological adhesion, and reproduction.ConclusionsFew associations were observed for scrotal circumference at 210 d of age, age at first calving, and age at second calving, reinforcing their polygenic inheritance and the complexity of understanding the genetic architecture of reproductive traits. Finding many associations for scrotal circumference at 420 d of age in various regions of the Canchim genome also reveals the difficulty of targeting specific candidate genes that could act on fertility; nonetheless, the high linkage disequilibrium between loci herein estimated could aid to overcome this issue. Therefore, all relevant information about genomic regions influencing reproductive traits may contribute to target candidate genes for further investigation of causal mutations and aid in future genomic studies in Canchim cattle to improve the breeding program.Electronic supplementary materialThe online version of this article (doi:10.1186/s40104-017-0199-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Candidate genes for male and female reproductive traits in Canchim beef cattle

Buzanskas

Grossi²,

Ventura

et al. 2017

J Animal Sci Biotechnol

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“…Mutations affecting the Eda pathway are known in medaka [ 13 ], zebrafish [ 14 ], mouse [ 4 , 6 , 8 ], cattle [ 15 - 18 ], dog [ 19 ], and human [ 3 , 5 , 6 ]. Of them, the mouse mutants have been widely characterized as a model organism of HED.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in some of the genes in the Eda pathway have been identified in various species, such as medaka [ 13 ], zebrafish [ 14 ], cattle [ 15 - 18 ], and dog [ 19 ]. Analyses of these mutations showed critical roles of the Eda pathway in the development of epithelial appendages, as well as in morphological evolution.…”

Section: Introductionmentioning

confidence: 99%

A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene

et al. 2011

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BackgroundHypohidrotic ectodermal dysplasia (HED) is a congenital disorder characterized by sparse hair, oligodontia, and inability to sweat. It is caused by mutations in any of three Eda pathway genes: ectodysplasin (Eda), Eda receptor (Edar), and Edar-associated death domain (Edaradd), which encode ligand, receptor, and intracellular adaptor molecule, respectively. The Eda signaling pathway activates NF-κB, which is central to ectodermal differentiation. Although the causative genes and the molecular pathway affecting HED have been identified, no curative treatment for HED has been established. Previously, we found a rat spontaneous mutation that caused defects in hair follicles and named it sparse-and-wavy (swh). Here, we have established the swh rat as the first rat model of HED and successfully identified the swh mutation.ResultsThe swh/swh rat showed sparse hair, abnormal morphology of teeth, and absence of sweat glands. The ectoderm-derived glands, meibomian, preputial, and tongue glands, were absent. We mapped the swh mutation to the most telomeric part of rat Chr 7 and found a Pro153Ser missense mutation in the Edaradd gene. This mutation was located in the death domain of EDARADD, which is crucial for signal transduction and resulted in failure to activate NF-κB.ConclusionsThese findings suggest that swh is a loss-of-function mutation in the rat Edaradd and indicate that the swh/swh rat would be an excellent animal model of HED that could be used to investigate the pathological basis of the disease and the development of new therapies.

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“…The ability to ameliorate or abolish congenital defects of HED using short-term treatment with recombinant ectodysplasin was first demonstrated in Tabby mice and refined in a canine model, leading to successful treatment of human fetuses [ 16 , 17 , 18 , 19 ]. To date, there are eight reported pathogenic variants of the bovine EDA gene that, result in an ECTD1-like disease (OMIA 000543-9913) [ 8 , 9 , 10 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. They are potentially lethal since affected cattle are ill-thrifty due to oligodontia and the heightened risk for pneumonia and hypothermia [ 20 , 21 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

X-Linked Hypohidrotic Ectodermal Dysplasia in Crossbred Beef Cattle Due to a Large Deletion in EDA

O’Toole

Häfliger

Leuthard

et al. 2021

Animals

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X-linked hypohidrotic ectodermal dysplasia-1 (ECTD1) in people results in a spectrum of abnormalities, most importantly hypotrichosis, anodontia/oligodontia, and absent or defective ectodermally derived glands. Five Red Angus-Simmental calves born over a 6-year period demonstrated severe hypotrichosis and were diagnosed as affected with ECTD1-like syndrome. Two died of severe pneumonia within a week of birth. The skin of three affected calves revealed a predominance of histologically unremarkable small-caliber hair follicles. Larger follicles (>50 µm) containing medullated hairs (including guard and tactile hairs) were largely restricted to the muzzle, chin, tail, eyelids, tragus and distal portions of the limbs and tail. The mean histological density of hair follicles in flank skin of two affected calves was slightly greater than that in two unaffected calves. One affected calf was examined postmortem at 10 days of age to better characterize systemic lesions. Nasolabial, intranasal and tracheobronchial mucosal glands were absent, whereas olfactory glands were unaffected. Mandibular incisor teeth were absent. Premolar teeth were unerupted and widely spaced. Other than oligodontia, histological changes in teeth were modest, featuring multifocal disorganization of ameloblasts, new bone formation in dental alveoli, and small aggregates of osteodentin and cementum at the margins of the enamel organ. A 52,780 base pair deletion spanning six out of eight coding exons of EDA and all of AWAT2 was identified. Partial deletion of the EDA gene is the presumed basis for the reported X-chromosomal recessive inherited genodermatosis.

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A novel point mutation within the EDA gene causes an exon dropping in mature RNA in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal dysplasia

Cited by 12 publications

References 23 publications

Candidate genes for male and female reproductive traits in Canchim beef cattle

Candidate genes for male and female reproductive traits in Canchim beef cattle

A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene

X-Linked Hypohidrotic Ectodermal Dysplasia in Crossbred Beef Cattle Due to a Large Deletion in EDA

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