The A-1 allele of the DRD2 gene is considered
the risk allele for antisocial phenotypes.
One recommendation is clear, regardless of the mode of inheritance: Two dogs carrying at least one copy of the IG - PRA1
risk allele should not be bred together.
OptiGen is able to provide updates on the actual frequency of
the risk allele in the population as more widespread testing of the breed occurs.
If so, it would be estimated that > 20 % of the Italian Greyhound population is likely to carry
the risk allele.
AFFECTED dogs carry two copies of the IG - PRA1
risk allele and thus have the genetic make - up that indicates they are at HIGH RISK to develop PRA due to the IG - PRA1
risk allele.
Another clear recommendation is that Italian Greyhounds that have been diagnosed clinically with PRA should not be bred, regardless of how many copies (0,1 or 2) of the IG - PRA1
risk allele they carry because it is possible that their PRA is due to another, as yet uncharacterized, form of PRA.
NORMAL dogs are at VERY LOW RISK of being affected with PRA associated with IG - PRA1
risk allele.
The majority of dogs in the research that carried only one copy of
the risk allele did not develop PRA.
CARRIERS may be at increased risk of developing PRA associated with IG - PRA1
risk allele.
At least one other form of PRA that is not associated with the IG - PRA1
risk allele is present in the Italian Greyhound.
Whether to breed Carriers of the IG - PRA1
risk allele is a difficult question to answer.
All Italian Greyhounds that were homozygous for the IG - PRA1
risk allele were diagnosed with PRA and two copies of the
risk allele were never observed in any Italian Greyhounds with normal eye exams (at the risk age or older).
It must be noted however that a subset of PRA - affected Italian Greyhounds in the study carried only one copy of the IG - PRA1
risk allele, suggesting that the disease may represent a mode of inheritance called «Autosomal Dominant with Incomplete Penetrance» (ADIP).
These dogs are very likely to develop PRA associated with the IG - PRA1
risk allele by the time they reach 5 - 7 years of age.
This could explain why some dogs that carry only one copy of the IG - PRA1
risk allele are diagnosed with PRA - they may be carrying two forms of the disease.
Advice on how to make best use of the DNA test for IG - PRA1 needs to account for the possibility that the disease may be inherited in an ADIP manner and that the presence of a single copy of
the risk allele may cause PRA in some Italian Greyhounds.
Polymorphisms in five of 15 genes (33 %) encoding molecules known to primarily influence pancreatic beta - cell function - ABCC8 (sulphonylurea receptor), KCNJ11 (KIR6.2), SLC2A2 (GLUT2), HNF4A (HNF4alpha), and INS (insulin)- significantly altered disease risk, and in three genes,
the risk allele, haplotype, or both had a biologically consistent effect on a relevant physiological trait in the QT study.
The impact of a common
risk allele with disease risk is often modest, as is its impact on clinical care.
The presence of a common
risk allele can indicate a need for increased surveillance, while a negative result implies a risk similar to the general population.
Given that two separate teams found evidence for the same variant in a large number of sick people, «one can be absolutely confident that
this risk allele is real,» says McPherson.
«The study also revealed that
the risk allele reduces the possibilities of reaching one hundred years of age.»
Because of this,
risk alleles are overrepresented among minor alleles.»
Around the world, innovative genomic - medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected
risk alleles or disease burdens.
No common BRCA mutations, no APOE
risk alleles.
If the ARMD and PGx variants were also considered, each individual carried 15.3
risk alleles on average.
Current collaborative efforts using germ line DNA to identify
risk alleles are ongoing.112 An improved understanding of the interaction between inherited
risk alleles and the environment (lifestyle choices) could provide a potential means of prevention.
Performing genetic studies in multiple human populations can identify disease
risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles.
These limitations can make the interpretation of common
risk alleles challenging.
The MAF of common
risk alleles can range from 5 % to 50 %.
Common
risk alleles are often detected by genome - wide association studies (GWAS) 1,2.
Further, there are currently no validated ways of combining multiple
risk alleles for the same disease.
Use of common
risk alleles for changes in clinical management can be challenging without a professional guideline.
Common
risk alleles with a known association with a condition can inform an individual of an increased or decreased risk of developing the condition in question; however, the degree of certainty is often unknown.
In addition, the clinical sensitivity of tests for common
risk alleles is not necessarily high.
Such strategies may identify compensatory mutations that reduce the pathophysiological effects of
the risk alleles, and help determine the cellular pathways required for the normal function of hSERT.
One approach, developed largely in collaboration with Dr. Elaine Ostrander at the National Human Genome Research Institute of the National Institutes of Health and Dr. Kerstin Lindblad - Toh at the Broad Institute of MIT and Harvard, seeks to map
risk alleles in Portuguese Water Dogs, Golden Retrievers, and German Shepherds using resources made available by the recent completion of the Canine Genome Project.
This tells us that heritability contributes to risk, and so it may be possible to reduce the incidence by eliminating the highest
risk alleles from the population.
The team will investigate whether bloat in German Shepherd Dogs is associated with the same
risk alleles and the same microbiome profiles as were seen in Great Danes.
The test identifies seven mutations in three different genes which permits identification of the «
risk alleles,» which are not causative of GDV but are highly associated.
Researchers at the Fred Hutchinson Cancer Research Center have identified three
risk alleles in three different genes associated with GDV in Great Danes.
Not exact matches
In some cases, we can actually trace that increased
risk to actual
alleles that segregate at different frequencies in different populations (eg., diabetes in Native American populations).
Individuals were classified as high
risk for Alzheimer's if a DNA test identified the presence of a genetic marker — having one or both of the apolipoprotein E-epsilon 4
allele (APOE - e4
allele) on chromosome 19 — which increases the
risk of developing the disease.
Within three weeks, they had collected the data that would fuel a series of landmark papers showing that the APOE4
allele is associated with a greatly increased
risk of Alzheimer's disease.
The obvious step, Roses realized, was to find out whether individual APOE
alleles influence the
risk of developing Alzheimer's disease.
Additional analysis of UK Biobank data from 112,338 people of European ancestry revealed that a specific form of rs9349379 known as the G
allele, which was present in 36 % of these individuals, was associated with an increased
risk of coronary artery disease.
Reviewing thousands of genome wide associate studies (GWAS) to identify genetic variants in single nucleotide polymorphisms (SNPs), investigators at Dartmouth's Norris Cotton Cancer Center found that some
alleles (one of a pair of genes located on a specific chromosome) are more frequently
risk - associated with disease than protective.
«With respect to disease,
alleles can be categorized into being
risk or protective ones.
Women with two copies of s fared even worse: They had bones that were 4 % less dense — and faced a 280 % higher
risk of fracture — than did women without any s
alleles, says team member Andre Uitterlinden, a molecular geneticist at Erasmus University in Rotterdam, the Netherlands.
«Carriers of this
allele had a roughly 2-fold increase in
risk for PTSD.»
The study found that among those at low
risk for depression, the «S» (short)
allele is associated with a thinner cortex than those with the «L» (long)
allele.