The number of mitochondrial DNA mutations as a genetic feature for hair cycle arrest (alopecia X) in Pomeranian dogs.

BACKGROUND Hair cycle arrest (HCA) is a noninflammatory alopecic disease affecting various dog breeds, particularly Pomeranian dogs. This disease is probably a hereditary disorder considering the strong breed predisposition. Despite efforts to identify the pathogenesis of this disease, an underlying specific cause is unknown. OBJECTIVE To identify candidate gene mutations for HCA in Pomeranian dogs. ANIMALS Four Pomeranian dogs diagnosed with HCA and four unaffected Pomeranian dogs. MATERIALS AND METHODS Whole blood was used for DNA extraction. Whole-genome sequencing (WGS) was performed, and variants were analysed using a Genome Analysis Toolkit (GATK) and SnpEff. All reads were aligned to the reference genome, Dog10K_Boxer_Tasha. Sanger sequencing was performed to define the complex mutations. RESULTS A total of 113 variants of mitochondrial DNA were found to be effective gene mutations in the eight dogs. The affected dogs showed significantly increased effective mutations (average 57 variants) compared with unaffected dogs (average eight variants; p < 0.05). There was no significant difference in the number of chromosomal DNA mutations between the two groups. CONCLUSION AND CLINICAL IMPORTANCE We suggest that an increased number of mitochondrial gene mutations are features for HCA in Pomeranian dogs.

[1]  M. Nöthen,et al.  Observations that suggest a contribution of altered dermal papilla mitochondrial function to androgenetic alopecia , 2022, Experimental dermatology.

[2]  C. Mellersh,et al.  Hereditary sensory and autonomic neuropathy in a family of mixed breed dogs associated with a novel RETREG1 variant , 2021, Journal of veterinary internal medicine.

[3]  J. Flowers,et al.  Origins and geographic diversification of African rice (Oryza glaberrima) , 2018, bioRxiv.

[4]  T. Schoeb,et al.  Reversing wrinkled skin and hair loss in mice by restoring mitochondrial function , 2018, Cell Death & Disease.

[5]  T. Leeb,et al.  Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X , 2017, PloS one.

[6]  Melissa Gymrek,et al.  A genomic view of short tandem repeats. , 2017, Current opinion in genetics & development.

[7]  A. Lenzi,et al.  Androgenetic alopecia: a review , 2017, Endocrine.

[8]  I. Soubeyran,et al.  The MAP3K ZAK, a novel modulator of ERK-dependent migration, is upregulated in colorectal cancer , 2016, Oncogene.

[9]  G. Johnson,et al.  Australian Cattle Dogs with Neuronal Ceroid Lipofuscinosis are Homozygous for a CLN5 Nonsense Mutation Previously Identified in Border Collies , 2016, Journal of veterinary internal medicine.

[10]  T. Bergström,et al.  Whole-Genome Sequencing of a Canine Family Trio Reveals a FAM83G Variant Associated with Hereditary Footpad Hyperkeratosis , 2016, G3: Genes, Genomes, Genetics.

[11]  S. Stoll,et al.  Microneedling as a successful treatment for alopecia X in two Pomeranian siblings. , 2015, Veterinary dermatology.

[12]  N. Larsson,et al.  Keeping mtDNA in Shape between Generations , 2014, PLoS genetics.

[13]  L. Vissers,et al.  Genome sequencing identifies major causes of severe intellectual disability , 2014, Nature.

[14]  E. Morrisey,et al.  Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. , 2013, Cell stem cell.

[15]  D. Morrison,et al.  MAP kinase pathways. , 2012, Cold Spring Harbor perspectives in biology.

[16]  T. Tumbar,et al.  Hairy tale of signaling in hair follicle development and cycling. , 2012, Seminars in cell & developmental biology.

[17]  J. Poderoso,et al.  Mitochondrial regulation of cell cycle and proliferation. , 2012, Antioxidants & redox signaling.

[18]  M. DePristo,et al.  The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. , 2010, Genome research.

[19]  J. Kvetny,et al.  Subclinical Hypothyroidism Affects Mitochondrial Function , 2010, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[20]  Robert W. Taylor,et al.  Mitochondrial DNA mutations and human disease. , 2010, Biochimica et biophysica acta.

[21]  Min-Xin Guan,et al.  Pathogenic mutations of nuclear genes associated with mitochondrial disorders. , 2009, Acta biochimica et biophysica Sinica.

[22]  Ruth Hershberg,et al.  Selection on codon bias. , 2008, Annual review of genetics.

[23]  C. Drögemüller,et al.  Exclusion of patched homolog 2 (PTCH2) as a candidate gene for alopecia X in pomeranians and keeshonden , 2008, Veterinary Record.

[24]  C. Drögemüller,et al.  Evaluation of the CTSL2 Gene as a Candidate Gene For Alopecia X in Pomeranians and Keeshonden , 2007, Animal biotechnology.

[25]  Wen-Hsiung Li,et al.  Intragenic Spatial Patterns of Codon Usage Bias in Prokaryotic and Eukaryotic Genomes , 2004, Genetics.

[26]  J. Oliver,et al.  Adrenal steroid hormone concentrations in dogs with hair cycle arrest (Alopecia X) before and during treatment with melatonin and mitotane. , 2004, Veterinary dermatology.

[27]  H. Evans,et al.  Treatment of canine Alopecia X with trilostane. , 2004, Veterinary dermatology.

[28]  N. Wright,et al.  Clinical features of dilated cardiomyopathy in Great Danes and results of a pedigree analysis: 17 cases (1990-2000). , 2001, Journal of the American Veterinary Medical Association.

[29]  P. Rompolas,et al.  Stem cell dynamics in the hair follicle niche. , 2014, Seminars in cell & developmental biology.

[30]  L. Medleau,et al.  Identifying and treating sex-hormone dermatoses in dogs. , 1990 .