Associated SNPsoutside of geneno effect on proteinproduction or function.TGAssociated SNPswithin geneno effect on proteinproduction or functionRegulatory sequencesACoding regionсTNoncoding SNP:changes amount ofprotein producedwww.Biolnteractive.orgCausative SNPswithin geneUnassociated SNPfar from geneon same chromosomeor different chromosomeProteinCoding SNP:changes aminoacid sequenceb. Which types of SNPs might be identified in a GWAS?4. Consider the different types of SNPs shown in Figure 3: associated, unassociated, and causative (includingboth noncoding and coding).a. Which types of SNPs affect protein production or function for the gene of interest?Figure 3. A diagramshowing various waysin which a SNP could beassociated with acertain gene and itstrait.GWAS in the NewsRead the following news release, which describes a GWAS study with dogs. Note that a dog's coat refers to itsfur or hair.Variants in Three Genes Account for Most Dog Coat DifferencesVariants in just three genes acting in different combinations account for the wide range of coat textures seen indogs from the poodle's tight curls to the beagle's stick-straight fur. A team led by researchers from theNational Human Genome Research Institute (NHGRI), part of the National Institutes of Health, reports thesefindings 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 biologicaldiversity," said NHGRI Scientific Director Eric Green, M.D., Ph.D. "Genomics continues to gain new insights fromthe amazing morphological differences seen across the canine species, including many that give clues abouthuman biology and disease."Until now, relatively little was known about the genes influencing the length, growth pattern and texture of thecoats of dogs. The researchers performed a genome-wide scan of specific signposts of DNA variation, calledsingle nucleotide polymorphisms, in 1,000 individual dogs representing 80 breeds. These data were comparedwith 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 howthey work together, rather than the genes themselves," said Elaine A. Ostrander, Ph.D., chief of the CancerGenetics Branch in NHGRI's Division of Intramural Research. "We think this approach will help pinpoint multiplegenes involved in complex human conditions, such as cancer, heart disease, diabetes and obesity."6. In two or three sentences, describe how scientists identified these genes.Updated November 2020Page 3 of 7hhmi BiolnteractiveMapping Genes to Traits in Dogs Using SNPsArtificial selection, at the heart of breeding for desirable traits in domesticated animals, hasyielded rapid change in a short span of canine history. While researchers estimate that modern dog breedsdiverged from wolves some 15,000 years ago, the genetic changes in the dog genome that create multiple coattypes 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.ActivityStudent HandoutModern 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 possiblegenetic variations. "When we put these genetic variants back together in different combinations, we found thatwe could create most of the coat varieties seen in what is among the most diverse species in the world thedog," Dr. Ostrander said. "If we can decipher the genetic basis for a complex trait such as the dog's coat, webelieve that we can do it as well with complex diseases."-Excerpt from a National Institutes of Health (NIH) News Release published August 27, 2009Answer the following questions to check your understanding of the reading.5. How many genes account for the wide variety of coat types in dogs?7. Why do you think it is important to analyze the DNA of many dogs when doing this research? Step 3Answer 4 a:SNPs that cause disease (noncoding and codingSNPs).Answer 4 b:In a GWAS, "any of the SNPs depicted in theimage might be found," and that only the relatedand causal SNPs are most likely to be linked tothe trait of interest.Step 4Answer 7:Finding variants that are often more prevalent indogs with a particular attribute compared todogs without that trait requires analyzing theDNA of many different dogs. It would be difficultto determine if variations in a small sample ofdogs are typically linked to the characteristic ofinterest rather than other features in those fewdogs if we simply looked at the variations inthose 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 ColorLet's explore how a GWAS works using a simple example that compares two groups of dogs: dogs with black furand dogs with white fur. Table 1 shows the dogs' SNP alleles at 17 specific locations in the genome. Thesespecific locations in the genome are called loci (singular: locus). The SNP alleles at each locus are represented bytwo 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).2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17CC AT CC GG AA TC TT CC GG AA TT GT AG AA CC GG AT*CC AT AC GG GG TT TT CC GG AG TT GG AG AG CC GG AT25CC AA AC CG GG TT TT CT GG AA TT GT AG AG CC TT ATwww.Biolnteractive.org5:3CC AA AC GG AG TT TT CT GG GG TT GG AG AG CC GT ATUpdated November 2020Page 4 of 6hhmi BiolnteractiveMapping Genes to Traits in Dogs Using SNPs231 CC AT CC CG| AATTAA CT GG AA TT GT AA AA CC GT ATActivityStudent HandoutCC AT CC GG AATTAA TC GG AA TT GG AGAA CC GG TTCC AT CC GG AATTAA CC GG AA TT GG AA AA CC GT ATCC AA CC GG AG TT AA TC GG GG TT GG AA AA CC TT ATIf a SNP is found much more frequently in dogs with white fur than in dogs with black fur, the SNP is associatedwith 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 thedogs with black fur to those of the dogs with white fur. A SNP is completely associated with fur color if alldogs with white fur share the same alleles at that position, and all dogs with black fur share different allelesat that position. A SNP that is completely associated with a trait is likely located within or close to a generesponsible for that trait.10. Which SNP in Table 1 do you think is completely associated with fur color? Explain the reasoning for yourchoice.A SNP is completely unassociated with fur color if its alleles occur with equal frequency in dogs with black furand dogs with white fur. A SNP that is completely unassociated with a trait is unlikely to be located within ornear the gene responsible for that trait.11. Which SNPs in Table 1 do you think are completely unassociated with fur color? Explain the reasoning foryour choices. (Hint: There are five in total.)The other SNPs in Table 1 have varying strengths of association with fur color. You'll learn more about how toevaluate the strength of an association in the next part of this activity. For the question below, make your bestguess based on what you've learned so far.12. Which SNP in Table 1 do you think has the next strongest association with fur color, after the completelyassociated SNP you identified in Question 10? Explain the reasoning for your choice.

Question

Associated SNPsoutside of geneno effect on proteinproduction or function.TGAssociated SNPswithin geneno effect on proteinproduction or functionRegulatory sequencesACoding regionсTNoncoding SNP:changes amount ofprotein producedwww.Biolnteractive.orgCausative SNPswithin geneUnassociated SNPfar from geneon same chromosomeor different chromosomeProteinCoding SNP:changes aminoacid sequenceb. Which types of SNPs might be identified in a GWAS?4. Consider the different types of SNPs shown in Figure 3: associated, unassociated, and causative (includingboth noncoding and coding).a. Which types of SNPs affect protein production or function for the gene of interest?Figure 3. A diagramshowing various waysin which a SNP could beassociated with acertain gene and itstrait.GWAS in the NewsRead the following news release, which describes a GWAS study with dogs. Note that a dog's coat refers to itsfur or hair.Variants in Three Genes Account for Most Dog Coat DifferencesVariants in just three genes acting in different combinations account for the wide range of coat textures seen indogs from the poodle's tight curls to the beagle's stick-straight fur. A team led by researchers from theNational Human Genome Research Institute (NHGRI), part of the National Institutes of Health, reports thesefindings today in the advance online issue of the journal Science.&#34;This study is an elegant example of using genomic techniques to unravel the genetic basis of biologicaldiversity,&#34; said NHGRI Scientific Director Eric Green, M.D., Ph.D. &#34;Genomics continues to gain new insights fromthe amazing morphological differences seen across the canine species, including many that give clues abouthuman biology and disease.&#34;Until now, relatively little was known about the genes influencing the length, growth pattern and texture of thecoats of dogs. The researchers performed a genome-wide scan of specific signposts of DNA variation, calledsingle nucleotide polymorphisms, in 1,000 individual dogs representing 80 breeds. These data were comparedwith descriptions of various coat types. Three distinct genetic variants emerged to explain, in combination,virtually all dog hair types.&#34;What's important for human health is the way we found the genes involved in dog coats and figured out howthey work together, rather than the genes themselves,&#34; said Elaine A. Ostrander, Ph.D., chief of the CancerGenetics Branch in NHGRI's Division of Intramural Research. &#34;We think this approach will help pinpoint multiplegenes involved in complex human conditions, such as cancer, heart disease, diabetes and obesity.&#34;6. In two or three sentences, describe how scientists identified these genes.Updated November 2020Page 3 of 7hhmi BiolnteractiveMapping Genes to Traits in Dogs Using SNPsArtificial selection, at the heart of breeding for desirable traits in domesticated animals, hasyielded rapid change in a short span of canine history. While researchers estimate that modern dog breedsdiverged from wolves some 15,000 years ago, the genetic changes in the dog genome that create multiple coattypes 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.ActivityStudent HandoutModern 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 possiblegenetic variations. &#34;When we put these genetic variants back together in different combinations, we found thatwe could create most of the coat varieties seen in what is among the most diverse species in the world thedog,&#34; Dr. Ostrander said. &#34;If we can decipher the genetic basis for a complex trait such as the dog's coat, webelieve that we can do it as well with complex diseases.&#34;-Excerpt from a National Institutes of Health (NIH) News Release published August 27, 2009Answer the following questions to check your understanding of the reading.5. How many genes account for the wide variety of coat types in dogs?7. Why do you think it is important to analyze the DNA of many dogs when doing this research? Step 3Answer 4 a:SNPs that cause disease (noncoding and codingSNPs).Answer 4 b:In a GWAS, &#34;any of the SNPs depicted in theimage might be found,&#34; and that only the relatedand causal SNPs are most likely to be linked tothe trait of interest.Step 4Answer 7:Finding variants that are often more prevalent indogs with a particular attribute compared todogs without that trait requires analyzing theDNA of many different dogs. It would be difficultto determine if variations in a small sample ofdogs are typically linked to the characteristic ofinterest rather than other features in those fewdogs if we simply looked at the variations inthose 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 ColorLet's explore how a GWAS works using a simple example that compares two groups of dogs: dogs with black furand dogs with white fur. Table 1 shows the dogs' SNP alleles at 17 specific locations in the genome. Thesespecific locations in the genome are called loci (singular: locus). The SNP alleles at each locus are represented bytwo 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).2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17CC AT CC GG AA TC TT CC GG AA TT GT AG AA CC GG AT*CC AT AC GG GG TT TT CC GG AG TT GG AG AG CC GG AT25CC AA AC CG GG TT TT CT GG AA TT GT AG AG CC TT ATwww.Biolnteractive.org5:3CC AA AC GG AG TT TT CT GG GG TT GG AG AG CC GT ATUpdated November 2020Page 4 of 6hhmi BiolnteractiveMapping Genes to Traits in Dogs Using SNPs231 CC AT CC CG| AATTAA CT GG AA TT GT AA AA CC GT ATActivityStudent HandoutCC AT CC GG AATTAA TC GG AA TT GG AGAA CC GG TTCC AT CC GG AATTAA CC GG AA TT GG AA AA CC GT ATCC AA CC GG AG TT AA TC GG GG TT GG AA AA CC TT ATIf a SNP is found much more frequently in dogs with white fur than in dogs with black fur, the SNP is associatedwith 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 thedogs with black fur to those of the dogs with white fur. A SNP is completely associated with fur color if alldogs with white fur share the same alleles at that position, and all dogs with black fur share different allelesat that position. A SNP that is completely associated with a trait is likely located within or close to a generesponsible for that trait.10. Which SNP in Table 1 do you think is completely associated with fur color? Explain the reasoning for yourchoice.A SNP is completely unassociated with fur color if its alleles occur with equal frequency in dogs with black furand dogs with white fur. A SNP that is completely unassociated with a trait is unlikely to be located within ornear the gene responsible for that trait.11. Which SNPs in Table 1 do you think are completely unassociated with fur color? Explain the reasoning foryour choices. (Hint: There are five in total.)The other SNPs in Table 1 have varying strengths of association with fur color. You'll learn more about how toevaluate the strength of an association in the next part of this activity. For the question below, make your bestguess based on what you've learned so far.12. Which SNP in Table 1 do you think has the next strongest association with fur color, after the completelyassociated SNP you identified in Question 10? Explain the reasoning for your choice.

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