One way to find SNPs associated with a certain trait is by comparing groups with different versions of that trait. In a GWAS looking for genes that affect dog fur color, for example, we could compare the SNPs of two groups: dogs with black fur and dogs with white fur. We would then determine which SNPs are significantly more common in dogs with black fur compared to dogs with white fur. These SNPs are "markers" for regions of the dog genome that contain genes affecting fur color. 3. Why do you think SNPs are referred to as "markers" or "signposts"? Figure 3 shows several possibilities for why a SNP is associated with a certain trait. The SNP may be in the gene that causes the trait or in a regulatory area for that gene. If so, the SNP could directly affect the gene's function and the resulting trait. However, some SNPs in or near a gene may have no effect on the gene or its trait. www.Biolnteractive.org hhmi BioInteractive Mapping Genes to Traits in Dogs Using SNPs Associated SNPs outside of gene a. no effect on protein production or function Associated SNPs within gene no effect on protein production or function Regulatory sequences Coding region с Noncoding SNP: changes amount of protein produced T Causative SNPs within gene Unassociated SNP far from gene on same chromosome or different chromosome Protein Coding SNP: changes amino acid sequence b. Which types of SNPs might be identified in a GWAS? T Updated November 2020 Page 2 of 7 Activity Student Handout 4. Consider the different types of SNPs shown in Figure 3: associated, unassociated, and causative (including both noncoding and coding). Which types of SNPs affect protein production or function for the gene of interest? Figure 3. A diagram showing various ways in which a SNP could be associated with a certain gene and its trait. 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." coats of Until now, relatively little was known about the genes influencing the length, growth pattern and texture of the . The researchers performed a genome-wide scan of ecific signposts of DNA 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

The beach mouse (Peromyscus polionotus) is a small rodent found in the southeastern United States. Coat color in the beach mouse is variable, from dark brown to blonde (Figure 1). A pigment called eumelanin is responsible for some of the diversity in mouse coat color. The MC1R gene, located on chromosome 8, plays a major role in the synthesis of eumelanin. There are two alleles of MC1R: R allele. Results in a functional MC1R protein that leads to stimulation of pigment production. This allele is found in dark colored mice. C allele. Results in a non-functional MC1R protein. Pigment production is, as a result, not stimulated. This allele is found in light colored mice.   Figure 1. Beach mouse with light fur (left) and dark (right). These mice are hunted by visual predators like owls and fox. The distribution of coat color is not random. Beach mice with dark fur are found further inland, on dark brown soils while mice with light fur are found on beaches, where the sand is light brown.…

The majority of GWAS associated variants exist in non-coding regions. This has led to additional challenges in understanding the biological mechanisms behind the trait, as the associated variants may not have a clear impact on gene function. Explain two non-coding mechanisms and how they contribute to genetic variation. In your answer, mention what types of sequencing data would assist in determining whether a non-coding GWAS locus may operate under these mechanisms.

The beach mouse (Peromyscus polionotus) is a small rodent found in the southeastern United States. Coat color in the beach mouse is variable, from dark brown to blonde (Figure 1). A pigment called eumelanin is responsible for some of the diversity in mouse coat color. The MC1R gene, located on chromosome 8, plays a major role in the synthesis of eumelanin. There are two alleles of MC1R: R allele. Results in a functional MC1R protein that leads to stimulation of pigment production. This allele is found in dark colored mice. C allele. Results in a non-functional MC1R protein. Pigment production is, as a result, not stimulated. This allele is found in light colored mice.   Figure 1. Beach mouse with light fur (left) and dark (right).           These mice are hunted by visual predators like owls and fox. The distribution of coat color is not random. Beach mice with dark fur are found further inland, on dark brown soils while mice with light fur are found on beaches, where the sand is…