Dog GWAS leads to a locus linked to digestive status in German Shepherds

NEW YORK – New research suggests that the number of repeat sequences in the MCHR2 gene encoding the ‘melanin-concentrating hormone receptor 2′ may inform German Shepherd dogs’ risk of developing a neuromuscular digestive disease called mega -congenital idiopathic esophagus (CIM), which affects swallowing, movement of food to the stomach, and survival of puppies.

“By identifying the primary genetic contributor to ICD in German Shepherds, we have provided breeders with a tool they can use to reduce disease incidence while preserving genetic diversity,” said lead author Leigh Anne. Clark, a genetics and biochemistry researcher at Clemson University. said in a statement.

For an article published in PLOS genetics On Thursday, researchers from Clemson University, the National Human Genome Research Institute and other centers in the US and UK initially took blood or buccal swab samples from 530 pet or pet dogs. assistance with or without CIM, incorporating phenotypic indices for over 750 additional German Shepherds.

In these groups of dogs, the team found that the condition was about twice as common in male German Shepherds, regardless of dog size, indicating a potential protective effect for females. Previous studies have shown that German Shepherds are at the most pronounced risk of CIM, although it has also been described in dogs of several other breeds ranging from Great Danes or Labrador Retrievers to Dachshunds and Mini Schnauzers.

The researchers then performed linkage disequilibrium analyzes and a genome-wide association study involving 59 German Shepherd dogs with CIM and 53 unaffected control dogs of the same breed, narrowing down to a CIM-linked locus. on chromosome 12 of the canine genome.

They then evaluated this locus in more detail with whole genome resequencing on three more affected female German Shepherds and available genome sequence data for over 1,300 other domestic dogs, focusing on a variable-number tandem repeat. of 33 base pairs (VNTR). in MCHR2 which was linked to an increased risk of CIM in German Shepherds.

Using genotyping data for hundreds of other dogs affected and unaffected by CIM, the team profiled allelic variants at this locus, before examining the possibility of predicting CIM based on MCHR2 VNTR genotypes. and biological sex.

“Together, sex and MCHR2 repeat sequence accurately predict disease status in more than 75% of dogs,” the authors reported, “and a genetic test is now available to aid in breeding decisions. aimed at reducing the incidence of the disease”.

The team noted that the CIM-linked repeat, which falls in the first intron of MCHR2, is most often present in two copies in wolves and other domestic dog breeds compared to one- or three-copy alleles. identified in most German Shepherds.

In German Shepherds, the risk of CIM was most closely related to the one-copy repeating allele, the researchers explained, particularly when that allele is present in both copies of the MCHR2 sequence. Since the VNTR spans a consensus binding sequence of the transcription factor T-box, they hypothesized that the binding sites might impact the expression of melanin-concentrating hormone activity. related to MCHR2 and CIM.

Based on their findings so far, the authors suggested that future research efforts may provide further insight into VNTR and gender-related risk of CIM and other gastrointestinal conditions in German Shepherds. and other dog breeds.

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