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? 6. In two or three sentences, describe how scientists identified these genes. 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?

Human Anatomy & Physiology (11th Edition)
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"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
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.
6. In two or three sentences, describe how scientists identified these genes.
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, we
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?
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).
2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
A
*
Updated November 2020
Page 3 of 7
Activity
Student Handout
303
CC AT CC GG AA TC TT CC GG AA TT GT AG AA CC GG AT
S
www.Biolnteractive.org
CC AT AC GG GG TT TT CC GG AG TT GG AG AG CC GG AT
CC AA AC CG GG TT TT CT GG AA TT GT AG AG CC TT AT
Shah
CC AA AC GG AG TT TT CT GG GG TT GG AG AG CC GT AT
Updated November 2020
Page 4 of 7
hhmi Biolnteractive
Mapping Genes to Traits in Dogs Using SNPs
CC AT CC CG AATTAA CT GG AA TT GT AA AA CC GT AT
Activity
Student Handout
CC AT CC GG AATTAA TC GG AA TT GG AG AA CC GG TT
CC AT CC GG AATTAA CC GG AA TT GG AA AA CC GT AT
CC AA CC GG AG TTAA TC GG GG TT GG AA AACC TT AT
Transcribed Image Text:"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 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. 6. In two or three sentences, describe how scientists identified these genes. 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, we 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? 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). 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 A * Updated November 2020 Page 3 of 7 Activity Student Handout 303 CC AT CC GG AA TC TT CC GG AA TT GT AG AA CC GG AT S www.Biolnteractive.org CC AT AC GG GG TT TT CC GG AG TT GG AG AG CC GG AT CC AA AC CG GG TT TT CT GG AA TT GT AG AG CC TT AT Shah CC AA AC GG AG TT TT CT GG GG TT GG AG AG CC GT AT Updated November 2020 Page 4 of 7 hhmi Biolnteractive Mapping Genes to Traits in Dogs Using SNPs CC AT CC CG AATTAA CT GG AA TT GT AA AA CC GT AT Activity Student Handout CC AT CC GG AATTAA TC GG AA TT GG AG AA CC GG TT CC AT CC GG AATTAA CC GG AA TT GG AA AA CC GT AT CC AA CC GG AG TTAA TC GG GG TT GG AA AACC TT AT
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.BioInteractive.org
hhmi BioInteractive
Mapping Genes to Traits in Dogs Using SNPs
Associated SNPs
outside of gene
a.
no effect on protein
production or function.
G
Associated SNPs
within gene
no effect on protein
production or function
Regulatory sequences
A
Coding region
с
T
Noncoding SNP:
changes amount of
protein produced
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?
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 journai 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
Transcribed Image Text: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.BioInteractive.org hhmi BioInteractive Mapping Genes to Traits in Dogs Using SNPs Associated SNPs outside of gene a. no effect on protein production or function. G Associated SNPs within gene no effect on protein production or function Regulatory sequences A Coding region с T Noncoding SNP: changes amount of protein produced 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? 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 journai 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
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