AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease
We investigated three related Rough Collies with recurrent inflammatory pulmonary disease. The clinical symptoms were similar to primary ciliary dyskinesia (PCD). However, the affected dogs did not carry any known pathogenic PCD variants. Pedigree analysis suggested a recessive mode of inheritance....
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ftmdpi:oai:mdpi.com:/2073-4425/10/8/567/ 2023-08-20T04:05:49+02:00 AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease Petra Hug Linda Anderegg Alexandra Kehl Vidhya Jagannathan Tosso Leeb agris 2019-07-26 application/pdf https://doi.org/10.3390/genes10080567 EN eng Multidisciplinary Digital Publishing Institute Animal Genetics and Genomics https://dx.doi.org/10.3390/genes10080567 https://creativecommons.org/licenses/by/4.0/ Genes; Volume 10; Issue 8; Pages: 567 Canis lupus familiaris dog whole genome sequence animal model AT-hook transcription factor immunology inflammation infection rare disease precision medicine Text 2019 ftmdpi https://doi.org/10.3390/genes10080567 2023-07-31T22:28:14Z We investigated three related Rough Collies with recurrent inflammatory pulmonary disease. The clinical symptoms were similar to primary ciliary dyskinesia (PCD). However, the affected dogs did not carry any known pathogenic PCD variants. Pedigree analysis suggested a recessive mode of inheritance. Combined linkage and homozygosity mapping in three cases and seven non-affected family members delineated 19 critical intervals on 10 chromosomes comprising a total of 99 Mb. The genome of one affected dog was sequenced and compared to 601 control genomes. We detected only a single private homozygous protein-changing variant in the critical intervals. The detected variant was a 4 bp deletion, c.2717_2720delACAG, in the AKNA gene encoding the AT-hook transcription factor. It causes a frame-shift introducing a premature stop codon and truncates 37% of the open reading frame, p.(Asp906Alafs*173). We genotyped 88 Rough Collies consisting of family members and unrelated individuals. All three available cases were homozygous for the mutant allele and all 85 non-affected dogs were either homozygous wildtype (n = 67) or heterozygous (n = 18). AKNA modulates inflammatory immune responses. Akna−/− knockout mice die shortly after birth due to systemic autoimmune inflammatory processes including lung inflammation that is accompanied by enhanced leukocyte infiltration and alveolar destruction. The perfect genotype-phenotype association and the comparative functional data strongly suggest that the detected AKNA:c.2717_2720delACAG variant caused the observed severe airway inflammation in the investigated dogs. Our findings enable genetic testing, which can be used to avoid the unintentional breeding of affected puppies. Text Canis lupus MDPI Open Access Publishing Genes 10 8 567 |
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Open Polar |
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MDPI Open Access Publishing |
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ftmdpi |
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English |
topic |
Canis lupus familiaris dog whole genome sequence animal model AT-hook transcription factor immunology inflammation infection rare disease precision medicine |
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Canis lupus familiaris dog whole genome sequence animal model AT-hook transcription factor immunology inflammation infection rare disease precision medicine Petra Hug Linda Anderegg Alexandra Kehl Vidhya Jagannathan Tosso Leeb AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease |
topic_facet |
Canis lupus familiaris dog whole genome sequence animal model AT-hook transcription factor immunology inflammation infection rare disease precision medicine |
description |
We investigated three related Rough Collies with recurrent inflammatory pulmonary disease. The clinical symptoms were similar to primary ciliary dyskinesia (PCD). However, the affected dogs did not carry any known pathogenic PCD variants. Pedigree analysis suggested a recessive mode of inheritance. Combined linkage and homozygosity mapping in three cases and seven non-affected family members delineated 19 critical intervals on 10 chromosomes comprising a total of 99 Mb. The genome of one affected dog was sequenced and compared to 601 control genomes. We detected only a single private homozygous protein-changing variant in the critical intervals. The detected variant was a 4 bp deletion, c.2717_2720delACAG, in the AKNA gene encoding the AT-hook transcription factor. It causes a frame-shift introducing a premature stop codon and truncates 37% of the open reading frame, p.(Asp906Alafs*173). We genotyped 88 Rough Collies consisting of family members and unrelated individuals. All three available cases were homozygous for the mutant allele and all 85 non-affected dogs were either homozygous wildtype (n = 67) or heterozygous (n = 18). AKNA modulates inflammatory immune responses. Akna−/− knockout mice die shortly after birth due to systemic autoimmune inflammatory processes including lung inflammation that is accompanied by enhanced leukocyte infiltration and alveolar destruction. The perfect genotype-phenotype association and the comparative functional data strongly suggest that the detected AKNA:c.2717_2720delACAG variant caused the observed severe airway inflammation in the investigated dogs. Our findings enable genetic testing, which can be used to avoid the unintentional breeding of affected puppies. |
format |
Text |
author |
Petra Hug Linda Anderegg Alexandra Kehl Vidhya Jagannathan Tosso Leeb |
author_facet |
Petra Hug Linda Anderegg Alexandra Kehl Vidhya Jagannathan Tosso Leeb |
author_sort |
Petra Hug |
title |
AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease |
title_short |
AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease |
title_full |
AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease |
title_fullStr |
AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease |
title_full_unstemmed |
AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease |
title_sort |
akna frameshift variant in three dogs with recurrent inflammatory pulmonary disease |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2019 |
url |
https://doi.org/10.3390/genes10080567 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes; Volume 10; Issue 8; Pages: 567 |
op_relation |
Animal Genetics and Genomics https://dx.doi.org/10.3390/genes10080567 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/genes10080567 |
container_title |
Genes |
container_volume |
10 |
container_issue |
8 |
container_start_page |
567 |
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1774716560670195712 |