Variant detection and runs of homozygosity in next generation sequencing data elucidate the genetic background of Lundehund syndrome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08-02

AUTHORS

Julia Metzger, Sophia Pfahler, Ottmar Distl

ABSTRACT

BACKGROUND: The Lundehund is a highly specialized breed characterized by a unique flexibility of the joints and polydactyly in all four limbs. The extremely small population size and high inbreeding has promoted a high frequency of diseased dogs affected by the Lundehund syndrome (LS), a severe gastro-enteropathic disease. RESULTS: Comprehensive analysis of bead chip and whole-genome sequencing data for LS in the Lundehund resulted in a genome-wide association signal on CFA 34 and LS-specific runs of homozygosity (ROH) in this region. Filtering analysis for variants with predicted high or moderate effects revealed a missense mutation in LEPREL1 1.2 Mb proximal to the region of the genome-wide association, which was shown to be significantly associated with LS. LS-affected Lundehund harbored the mutant LEPREL1:g.139212C>G genotype A/A whereas all controls of other breeds showed the C/C wild type. In addition, ROH analysis for the Lundehund indicated a high enrichment of genes in potential signatures of selection affecting protein activation and immunoregulatory processes like NOD1 potentially involved in LS breed disposition. CONCLUSIONS: Sequencing results for Lundehund specific traits reveal a potential causative mutation for LS in the neuropeptide operating gene LEPREL1 and suggests it as a precursor of the inflammatory process. Analyses of ROH regions give an insight into the genetic background of characteristic traits in the Lundehund that remain to be elucidated in the future. More... »

PAGES

535

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12864-016-2844-6

DOI

http://dx.doi.org/10.1186/s12864-016-2844-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009049075

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27485430


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