Intronic variant in POU1F1 associated with canine pituitary dwarfism.
Animals
Breeding
Dog Diseases
/ genetics
Dogs
Dwarfism, Pituitary
/ genetics
Exons
Female
Genome-Wide Association Study
Heterozygote
High-Throughput Nucleotide Sequencing
Homozygote
Hypopituitarism
/ genetics
Introns
Male
Mutation
Pedigree
RNA Splicing
Transcription Factor Pit-1
/ genetics
Whole Genome Sequencing
Journal
Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
21
12
2020
accepted:
25
01
2021
pubmed:
8
2
2021
medline:
31
10
2021
entrez:
7
2
2021
Statut:
ppublish
Résumé
The anterior pituitary gland secretes several endocrine hormones, essential for growth, reproduction and other basic physiological functions. Abnormal development or function of the pituitary gland leads to isolated or combined pituitary hormone deficiency (CPHD). At least 30 genes have been associated with human CPHD, including many transcription factors, such as POU1F1. CPHD occurs spontaneously also in mice and dogs. Two affected breeds have been reported in dogs: German Shepherds with a splice defect in the LHX3 gene and Karelian Bear Dogs (KBD) with an unknown genetic cause. We obtained samples from five KBDs presenting dwarfism and abnormal coats. A combined analysis of genome-wide association and next-generation sequencing mapped the disease to a region in chromosome 31 and identified a homozygous intronic variant in the fourth exon of the POU1F1 gene in the affected dogs. The identified variant, c.605-3C>A, resided in the splice region and was predicted to affect splicing. The variant's screening in three new prospective cases, related breeds, and ~ 8000 dogs from 207 breeds indicated complete segregation in KBDs with a carrier frequency of 8%, and high breed-specificity as carriers were found at a low frequency only in Lapponian Herders, a related breed. Our study establishes a novel canine model for CPHD with a candidate POU1F1 defect.
Identifiants
pubmed: 33550451
doi: 10.1007/s00439-021-02259-2
pii: 10.1007/s00439-021-02259-2
pmc: PMC8519942
doi:
Substances chimiques
Transcription Factor Pit-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1553-1562Informations de copyright
© 2021. The Author(s).
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