Genomic Inbreeding and Selection Signatures analyses in the Doberman Pinscher breed

Abstract

The Doberman Pinscher population has undergone strong artificial selection for morphology and behavior, which can reduce genomic diversity and increase autozygosity. Here, we characterized the genome structure and identified selection signatures in Doberman Pinschers using complementary within- and between-population approaches. Genotypes from 3,226 Dobermans Dogs (Illumina CanineHD; 216,184 SNPs) provided by the Doberman Diversity Project were analyzed after purpose-specific quality control. Genomic inbreeding was quantified using four allele-frequency-based metrics and the runs of homozygosity (FROH) approach. Selection signatures were detected using intrapopulation (i.e., Runs of Homozygosity--ROH; Integrated Haplotype Score--iHS; and Number of Segregating Sites by Length--nSL) and interpopulation methods (i.e., Fixation Index--FST; Cross-Population Extended Haplotype Homozygosity--XP-EHH; and Cross-Population Number of Segregating Sites by Length--XP-nSL) comparing the Doberman Pinscher breed to Labrador Retriever (n=237). Dobermans showed high overall inbreeding, with a mean FROH of 0.42 (range 0.22-0.68), whereas the allele-frequency-based inbreeding estimators had similar means ([~]0.04). The partitioning of the ROH indicated high contributions from medium-to-long ROHs, consistent with recent inbreeding. The ROH scans identified 39,512 SNPs in ROH islands ([≥]50% frequency across individuals), with notable concentrations on CFA2, CFA3, and CFA31. Haplotype-based scans identified 2,820 candidate iHS SNPs and 2,173 candidate nSL SNPs (|score|>2). A common set of 310 SNPs was shared among ROH, iHS, and nSL, mapping near 279 genes that were mostly enriched for developmental pathways, particularly neurodevelopment and neuron-related cellular components. Between breeds, 349 highly differentiated SNPs were detected by FST, while XP-EHH and XP-nSL highlighted over 1,000 of Doberman-specific haplotype signals. A total of seven SNPs overlapped across FST, XP-EHH, and XP-nSL, which were located mainly on CFA8 ([~]59.48-60.61 Mb) near the KCNK10, SPATA7, PTPN21, NEGR1, and BTG1 genes. These genes are mainly linked to neural development and signaling, but BTG1 has also been associated with cardiomyocyte cell-cycle regulation, and KCNK10 with cardiac excitability and remodeling. Overall, the Doberman Pinscher breed exhibits high genome-wide autozygosity and levels of inbreeding. In addition, our results showed consistent, multi-method evidence of selection at loci associated with neurodevelopmental and regulatory pathways. These findings provide prioritized targets for follow-up studies that integrate phenotypes relevant to breed health and performance.