Correlations and standard multiple regression of variables on dependent variable (DV) Total Activity.

<p><i>p</i>< = 0.05; **<i>p</i>< = 0.01.</p

Breed Distributions for dogs included in activity study.

<p>Breed Distributions for dogs included in activity study.</p

Differences in Behavior and Activity Associated with a Poly(A) Expansion in the Dopamine Transporter in Belgian Malinois

<div><p>In Belgian Malinois dogs, a 38-base pair variable number tandem repeat in the dopamine transporter gene (<i>SLC6A3</i>) is associated with behavior changes in Malinois. By additional sequencing in <i>SLC6A3</i>, we identified an intronic 12-nucleotide poly(A) insertion (“PolyA(22)”) before the terminal exon that was associated with seizure, “glazing over” behaviors, and episodic biting behaviors in a sample of 138 Malinois. We next investigated whether PolyA(22) was associated with 1) increased locomotor activity and 2) response to novelty. Using a sample of 22 Malinois and 25 dogs of other breeds, dogs’ activity was monitored in a novel and non-novel environment while wearing activity monitoring collars. All dogs were more active in novel compared with non-novel environments, and Malinois were more active overall than other breeds. There was an effect of PolyA(22) genotype on activity levels, and this effect appeared to underlie the difference detected between Malinois and other breeds. There was no effect of PolyA(22) genotype on the relative decrease in activity between novel and non-novel environments for either group or all dogs considered together. In addition to an association between PolyA(22) and owner reports of seizure, “glazing over” behaviors, and episodic biting behaviors, these findings support an effect of PolyA(22) on dopamine transporter function related to activity. Further investigation is required to confirm mechanistic effects of PolyA(22) on <i>SLC6A3</i>. The complex polygenic nature of behavior and the range of behaviors associated with this insertion predict that effects are likely also modified by additional genetic and environmental factors.</p></div

PolyA alleles and owner-reported loss of responsiveness to environmental stimuli (“glazing over”).

<p>Glazing over: Distribution for number of PolyA(22) alleles (0: Malinois with no PolyA(22) alleles; 1: Malinois with one PolyA(22) allele; 2: Malinois homozygous for PolyA(22)) for owners only reporting dogs’ eyes “glazing over”. *: <i>p</i><0.05.</p

PolyA alleles and activity differences.

<p>Activity differences: Mean total activity for number of PolyA(22) alleles (0: dogs with no PolyA(22) alleles; 1: dogs with one PolyA(22) allele; 2: dogs homozygous for PolyA(22)) (Malinois and other breeds combined) (*<i>p</i><0.05).</p

PolyA(22) genotype by Malinois/Other for dogs in activity study.

<p>PolyA(22) genotype by Malinois/Other for dogs in activity study.</p

Three alleles at polyA site.

<p>Allele differences beginning at chr34∶11243915 (Broad CanFam3.1) for Boxer reference sequence (“polyA(10)”), the allele most common in other breeds in our dataset (g.34805del(18); “polyA(0)”), and the allele (g.34805A(12); “PolyA(22)”) found primarily in Malinois in our dataset.</p

data_123801SNP

data_123801SN

Percentages and number of cases over the total sample size for each neutering status group; intact and neutered early or late for female Golden Retrievers (1–8 years old) diagnosed with hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and/or mast cell tumor (MCT) at the Veterinary Medical Teaching Hospital of the University of California, Davis, from 2000–2009.

<p>For CCL the difference between intact and early-neutered was statistically significant (K-M). For HSA, the differences between early and late-neutered and intact and late-neutered groups were statistically significant (RR), as were differences for MCT between early and late-neutered groups. A similar statistical comparison for late neutering and intact groups was not possible for MCT because there were 0 cases in the intact group.</p

Categories used in determining diagnosis for joint disorders and cancers of interest in Golden Retrievers (1–8 years old) admitted to the Veterinary Medical Hospital, University of California, Davis, from 2000–2009.

<p>Categories used in determining diagnosis for joint disorders and cancers of interest in Golden Retrievers (1–8 years old) admitted to the Veterinary Medical Hospital, University of California, Davis, from 2000–2009.</p