## Educational Website Content### Understanding SNPs and GWAS in Canines#### SNP Diagram OverviewFigure 3 in the diagram illustrates various ways a Single Nucleotide Polymorphism (SNP) can be associated with a specific gene and its trait. It presents different types of SNPs:- **Associated SNPs outside the gene:** These have no impact on protein production or function.- **Associated SNPs within the gene:** They may or may not affect protein production or function.- **Unassociated SNP far from the gene:** Located on the same or different chromosomes, not affecting the gene directly.- **Causative SNPs within the gene:** - **Noncoding SNP:** Changes the amount of protein produced. - **Coding SNP:** Alters the amino acid sequence.#### Questions for Understanding1. **Consider the different types of SNPs shown in Figure 3: associated, unassociated, and causative (including both noncoding and coding).** - **a. Which types of SNPs affect protein production or function for the gene of interest?** *(Answer space provided)* - **b. Which types of SNPs might be identified in a GWAS?** *(Answer space provided)*#### GWAS in the NewsA news release discusses a Genome-Wide Association Study (GWAS) on dogs, focusing on their coat characteristics such as fur or hair.**Title: Variants in Three Genes Account for Most Dog Coat Differences**- Genetic variants in three specific genes influence a wide range of dog fur textures, from poodle curls to beagle straightness.- Research led by the National Human Genome Research Institute (NHGRI) found these results, published in *Science*.- Historically, knowledge about the genetics of dog coat types was limited. The study used a genome-wide scan in 1,000 dogs covering 80 breeds, identifying three significant genetic variations that explain most coat variations.**Comments by Scientists:**- Dr. Eric Green emphasized the potential of genomics to reveal biological diversity.- Dr. Elaine A. Ostrander highlighted the implications for understanding complex diseases in humans through these genetic insights.**Source:** National Institutes of Health (NIH) News Release, August 27, 2009.#### Comprehension Questions5. **How many genes account for the wide variety of coat types in dogs?** *(Answer space provided)*6. Step 3**Answer 4 a:**SNPs that cause disease (noncoding and coding SNPs).**Answer 4 b:**In a GWAS, "any of the SNPs depicted in the image might be found," and that only the related and causal SNPs are most likely to be linked to the trait of interest.Step 4**Answer 7:**Finding variants that are often more prevalent in dogs with a particular attribute compared to dogs without that trait requires analyzing the DNA of many different dogs. It would be difficult to determine if variations in a small sample of dogs are typically linked to the characteristic of interest rather than other features in those few dogs if we simply looked at the variations in those few dogs.**7.** Why do you think it is important to analyze the DNA of many dogs when doing this research?**8.** Humans have SNPs too. In general, how might GWAS studies with dogs benefit humans?---**PART 2: Applying GWAS to Dog Fur Color**Let’s explore how a GWAS works using a simple example that compares two groups of dogs: dogs with black fur and dogs with white fur. Table 1 shows the dogs’ SNP alleles at 17 specific locations in the genome. These specific locations in the genome are called loci (singular: locus). The SNP alleles at each locus are represented by two nucleotides, one from each parental chromosome.**Table 1. SNP alleles at 17 different loci in dogs with black fur (first four rows) and dogs with white fur (last four rows).**[Table showing genotype data for dogs]If a SNP is found much more frequently in dogs with white fur than in dogs with black fur, the SNP is associated with the white fur color.**9.** Give two possible reasons for why a SNP would be associated with a trait like fur color.To determine whether any of the SNPs in Table 1 are associated with fur color, you can compare the SNPs of the dogs with black fur to those of the dogs with white fur. A SNP is completely associated with fur color if all dogs with white fur share the same alleles at that position, and all dogs with black fur share different alleles at that position. A SNP that is completely associated with a trait is likely located within or close to a gene responsible for that trait.**10.** Which SNP in Table 1 do

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4. Consider the different types of SNPs shown in Figure 3: associated, unassociated, and causative (including both noncoding and coding). a. Which types of SNPs affect protein production or function for the gene of interest? b. Which types of SNPs might be identified in a GWAS? GWAS in the News Read the following news release, which describes a GWAS study with dogs. Note that a dog's coat refers to its fur or hair. Variants in Three Genes Account for Most Dog Coat Differences Variants in just three genes acting in different combinations account for the wide range of coat textures seen in dogs from the poodle's tight curls to the beagle's stick-straight fur. A team led by researchers from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, reports these findings today in the advance online issue of the journal Science. "This study is an elegant example of using genomic techniques to unravel the genetic basis of biological diversity," said NHGRI Scientific Director Eric Green, M.D., Ph.D. "Genomics continues to gain new insights from the amazing morphological differences seen across the canine species, including many that give clues about human biology and disease." Until now, relatively little was known about the genes influencing the length, growth pattern and texture of the coats of dogs. The researchers performed a genome-wide scan of specific signposts of DNA variation, called single nucleotide polymorphisms, in 1,000 individual dogs representing 80 breeds. These data were compared with descriptions of various coat types. Three distinct genetic variants emerged to explain, in combination, virtually all dog hair types. "What's important for human health is the way we found the genes involved in dog coats and figured out how they work together, rather than the genes themselves," said Elaine A. Ostrander, Ph.D., chief of the Cancer Genetics Branch in NHGRI's Division of Intramural Research. "We think this approach will help pinpoint multiple genes involved in complex human conditions, such as cancer, heart disease, diabetes and obesity." www.Biolnteractive.org Updated November 2020 Page 3 of 7 Activity Student Handout hhmi Biolnteractive Mapping Genes to Traits in Dogs Using SNPs Artificial selection, at the heart of breeding for desirable traits in domesticated animals, has yielded rapid change in a short span of canine history. While researchers estimate that modern dog breeds diverged from wolves some 15,000 years ago, the genetic changes in the dog genome that create multiple coat types are more likely to have been pursued by breeders in just the past 200 years. In fact, short-haired breeds, such as the beagle, display the original, more wolf-like versions of the three genes identified in the study. Modern dog breeds are part of a unique population structure, having been selectively bred for many years. Based on this structure, the researchers were able to break down a complex phenotype-coat - into possible genetic variations. "When we put these genetic variants back together in different combinations, we found that we could create most of the coat varieties seen in what is among the most diverse species in the world the dog," Dr. Ostrander said. "If we can decipher the genetic basis for a complex trait such as the dog's coat, wel believe that we can do it as well with complex diseases." -Excerpt from a National Institutes of Health (NIH) News Release published August 27, 2009 Answer the following questions to check your understanding of the reading. 5. How many genes account for the wide variety of coat types in dogs?