Partial Deletion of the Bovine <i>ED1</i> Gene Causes Anhidrotic Ectodermal Dysplasia in Cattle

Drögemüller, Cord; Distl, O.; Leeb, Tosso

doi:10.1101/gr.182501

Cited by 71 publications

(94 citation statements)

References 20 publications

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“…Many similar mutations in exon 1 have been described in humans (Kere et al 1996;Bayés et al 1998;Ferguson et al 1998;Hertz et al 1998;Paakkonen et al 2001;Schneider et al 2001). In black and white German Holstein cattle with XHED, a large genomic deletion that included all of exon 3 caused a frame shift and a premature stop codon resulting in a severely truncated ectodysplasin (Drögemüller et al 2001). In humans, a single case of XHED with the complete deletion of exon 3 has been described (Bayes et al The mutation found in canine EDA confirmed its involvement in XHED in our dog model.…”

Section: Discussionsupporting

confidence: 64%

Mutation identification in a canine model of X-linked ectodermal dysplasia

et al. 2005

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X-linked hypohidrotic ectodermal dysplasia (XHED), an inherited disease recognized in humans, mice, and cattle, is characterized by hypotrichosis, a reduced number or absence of sweat glands, and missing or malformed teeth. In a subset of affected individuals and animals, mutations in the EDA gene (formerly EDI), coding for ectodysplasin, have been found to cause this phenotype. Ectodysplasin is a homotrimeric transmembrane protein with an extracellular TNF-like domain, which has been shown to be involved in the morphogenesis of hair follicles and tooth buds during fetal development. Some human XHED patients also have concurrent immunodeficiency, due to mutations in the NF-κB essential modulator protein (IKBKG; formerly NEMO), which is also encoded on the X chromosome. In a breeding colony of dogs with XHED, immune system defects had been suspected because of frequent pulmonary infections and unexpected deaths resulting from pneumonia. To determine if defects in EDA or IKBKG cause XHED in the dogs, linkage analysis and sequencing experiments were performed. A polymorphic marker near the canine EDA gene showed significant linkage to XHED. The canine EDA gene was sequenced and a nucleotide substitution (G to A) in the splice acceptor site of intron 8 was detected in affected dogs. In the presence of the A residue, a cryptic acceptor site within exon 9 is used, leading to a frame shift and use of a premature stop codon that truncates the translation of both isoforms, EDA-A1 and EDA-A2, resulting in the absence of the TNF-like homology domain, the receptorbinding site of ectodysplasin.

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Section: Discussionsupporting

confidence: 64%

Mutation identification in a canine model of X-linked ectodermal dysplasia

et al. 2005

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“…The chicken peacomb phenotype was linked to a duplication near the first intron of SOX5 (Wright et al 2009). Similarly, partial deletion of the bovine gene ED1 causes anhidrotic ectodermal dysplasia in cattle (Drogemuller et al 2001). Given the heritability of CNVs and their higher rates of mutation, it is possible that CNVs may be associated with or affect animal health and production traits under recent selection.…”

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confidence: 99%

Copy number variation of individual cattle genomes using next-generation sequencing

Bickhart¹,

Hou²,

Schroeder³

et al. 2012

Genome Res.

278

310

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Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one Holstein, and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1265 CNV regions comprising~55.6-Mbp sequence-476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with array comparative genomic hybridization (aCGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH), achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (~52%, x 2 test; P-value <0.05). In contrast, genes related to pathogen-and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and

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“…Corresponding spontaneous mutant animal models for EDA pathway genes have thus far been identified in four species: Edar mutant medaka fish; Eda mutant dogs and cattle; and the Tabby, Downless/Sleek and Crinkled mouse mutants. 8,9,13,[18][19][20] The skin appendages are often species-specific, so that in contrast to the effects on hair and sweat glands in mammals, fish show a loss of scales. 18 In a recent study, the EDA gene was shown to be involved in adaptive evolution of armor plate patterning in three-spine stickleback fishes during the transition from marine to freshwater environment.…”

Section: Eda Signaling Pathway Is Highly Conserved During Evolutionmentioning

confidence: 99%