Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia
Abstract Background In mammals, hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that is characterized by sparse hair, tooth abnormalities, and defects in cutaneous glands. Only four genes, EDA, EDAR, EDARADD and WNT10A account for more than 90% of HED cases, and EDA, on chromosome X, i...
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-019-6087-1 |
| _version_ | 1818872815891251200 |
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| author | Clémentine Escouflaire Emmanuelle Rebours Mathieu Charles Sébastien Orellana Margarita Cano Julie Rivière Cécile Grohs Hélène Hayes Aurélien Capitan |
| author_facet | Clémentine Escouflaire Emmanuelle Rebours Mathieu Charles Sébastien Orellana Margarita Cano Julie Rivière Cécile Grohs Hélène Hayes Aurélien Capitan |
| author_sort | Clémentine Escouflaire |
| collection | DOAJ |
| description | Abstract Background In mammals, hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that is characterized by sparse hair, tooth abnormalities, and defects in cutaneous glands. Only four genes, EDA, EDAR, EDARADD and WNT10A account for more than 90% of HED cases, and EDA, on chromosome X, is involved in 50% of the cases. In this study, we explored an isolated case of a female Holstein calf with symptoms similar to HED. Results Clinical examination confirmed the diagnosis. The affected female showed homogeneous hypotrichosis and oligodontia as previously observed in bovine EDAR homozygous and EDA hemizygous mutants. Under light microscopy, the hair follicles were thinner and located higher in the dermis of the frontal skin in the affected animal than in the control. Moreover, the affected animal showed a five-fold increase in the number of hair follicles and a four-fold decrease in the diameter of the pilary canals. Pedigree analysis revealed that the coefficient of inbreeding of the affected calf (4.58%) was not higher than the average population inbreeding coefficient (4.59%). This animal had ten ancestors in its paternal and maternal lineages. By estimating the number of affected cases that would be expected if any of these common ancestors carried a recessive mutation, we concluded that, if they existed, other cases of HED should have been reported in France, which is not the case. Therefore, we assumed that the causal mutation was dominant and de novo. By analyzing whole-genome sequencing data, we identified a large chromosomal inversion with breakpoints located in the first introns of the EDA and XIST genes. Genotyping by PCR-electrophoresis the case and its parents allowed us to demonstrate the de novo origin of this inversion. Finally, using various sources of information we present a body of evidence that supports the hypothesis that this mutation is responsible for a skewed inactivation of X, and that only the normal X can be inactivated. Conclusions In this article, we report a unique case of X-linked HED affected Holstein female calf with an assumed full inactivation of the normal X-chromosome, thus leading to a severe phenotype similar to that of hemizygous males. |
| first_indexed | 2024-12-19T12:44:49Z |
| format | Article |
| id | doaj.art-8f27ea9365cd4d0c80e877f60afa6c7a |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-19T12:44:49Z |
| publishDate | 2019-09-01 |
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| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-8f27ea9365cd4d0c80e877f60afa6c7a2022-12-21T20:20:49ZengBMCBMC Genomics1471-21642019-09-0120111110.1186/s12864-019-6087-1Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasiaClémentine Escouflaire0Emmanuelle Rebours1Mathieu Charles2Sébastien Orellana3Margarita Cano4Julie Rivière5Cécile Grohs6Hélène Hayes7Aurélien Capitan8INRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayINRA, GABI, AgroParisTech, Université Paris-SaclayAbstract Background In mammals, hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that is characterized by sparse hair, tooth abnormalities, and defects in cutaneous glands. Only four genes, EDA, EDAR, EDARADD and WNT10A account for more than 90% of HED cases, and EDA, on chromosome X, is involved in 50% of the cases. In this study, we explored an isolated case of a female Holstein calf with symptoms similar to HED. Results Clinical examination confirmed the diagnosis. The affected female showed homogeneous hypotrichosis and oligodontia as previously observed in bovine EDAR homozygous and EDA hemizygous mutants. Under light microscopy, the hair follicles were thinner and located higher in the dermis of the frontal skin in the affected animal than in the control. Moreover, the affected animal showed a five-fold increase in the number of hair follicles and a four-fold decrease in the diameter of the pilary canals. Pedigree analysis revealed that the coefficient of inbreeding of the affected calf (4.58%) was not higher than the average population inbreeding coefficient (4.59%). This animal had ten ancestors in its paternal and maternal lineages. By estimating the number of affected cases that would be expected if any of these common ancestors carried a recessive mutation, we concluded that, if they existed, other cases of HED should have been reported in France, which is not the case. Therefore, we assumed that the causal mutation was dominant and de novo. By analyzing whole-genome sequencing data, we identified a large chromosomal inversion with breakpoints located in the first introns of the EDA and XIST genes. Genotyping by PCR-electrophoresis the case and its parents allowed us to demonstrate the de novo origin of this inversion. Finally, using various sources of information we present a body of evidence that supports the hypothesis that this mutation is responsible for a skewed inactivation of X, and that only the normal X can be inactivated. Conclusions In this article, we report a unique case of X-linked HED affected Holstein female calf with an assumed full inactivation of the normal X-chromosome, thus leading to a severe phenotype similar to that of hemizygous males.http://link.springer.com/article/10.1186/s12864-019-6087-1Hypohidrotic ectodermal dysplasiaEDAXISTWhole-genome sequencingHolsteinCattle |
| spellingShingle | Clémentine Escouflaire Emmanuelle Rebours Mathieu Charles Sébastien Orellana Margarita Cano Julie Rivière Cécile Grohs Hélène Hayes Aurélien Capitan Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia BMC Genomics Hypohidrotic ectodermal dysplasia EDA XIST Whole-genome sequencing Holstein Cattle |
| title | Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia |
| title_full | Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia |
| title_fullStr | Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia |
| title_full_unstemmed | Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia |
| title_short | Α de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia |
| title_sort | α de novo 3 8 mb inversion affecting the eda and xist genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia |
| topic | Hypohidrotic ectodermal dysplasia EDA XIST Whole-genome sequencing Holstein Cattle |
| url | http://link.springer.com/article/10.1186/s12864-019-6087-1 |
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