Transcript Human Genetics

Chapter 7
Multifactorial
Traits
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Learning Outcomes
• Distinguish between single-gene and polygenic
traits
• Define multifactorial traits
• Explain how continuously varying traits reflect
genes and the environment
• Explain how empiric risk differs from calculating
a Mendelian frequency
• Define heritability
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Learning Outcomes
• Discuss what studies on adopted individuals and
twins can reveal
• Explain what a genome-wide association study
can reveal
• Discuss tools and approaches used to study body
weight
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Genes, Environment and Traits
• Few genes act alone
• Environmental factors and other genes may
modify expression
• Traits can be described as
• Mendelian - Caused by a single gene
• Polygenic - Caused by multiple genes
• Both can be multifactorial or complex due to an
interaction between genes and the environment
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Genes, Environment and Traits
• Single-gene traits are discrete or qualitative
• Often produce an all-or-none effect
• Polygenic traits produce a continuously varying
phenotype
• Also called quantitative traits
• DNA sequences involved are termed Quantitative
Trait Loci (QTLs)
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Genes, Environment and Traits
Lung Cancer Risks
Reduced DNA Repair
Promote inflammation
Blocking detoxificaton of
carcinogens
Keeping telomers long
Promoting addition
Genes Interact with the
environment ex.smoking
and or breathing polluted
air
Figure 7.1
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Polygenic Traits
• Influenced by interaction of genes and by the
environment
• Examples
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Height
Skin color
Body weight
Fingerprint patterns
Behavioral traits
Migraine
Heart Health
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Polygenic Traits
• Individual genes follow Mendel’s laws, but their
expression is hard to predict
• Effect of genes is additive or synergistic
• Input of genes is not necessarily identical
• Frequency of distribution of phenotypes forms a
bell-shaped curve
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Fingerprint Patterns
• Dermatoglyphics is the study of fingerprints
• Number of ridges is largely determined by genes
and prenatal contact
• Average total ridge count is 145 in a male and 126
in a female
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Fingerprint Patterns
Figure 7.2
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Height
Figure 7.3
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Height
• Difference in height between the students of the
yester years and today are attributed to improved
diet and better overall health
• Genome-wide association studies have identified
dozens of genes that affect height
• Certain SNPs patterns are seen in individuals with
periods of rapid height increase
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Skin Color
• Melanin protects against DNA damage from UV
radiation, and exposure to the sun increases
melanin synthesis
• Humans have same number of melanocytes per
unit area of skin
• Differ in melanosome number, size and density
distribution
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Skin Color
Figure 7.4
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Skin Color
• Definition of race based largely on skin color is a
social construct more than a biological concept
• Skin color is not a reliable indicator of ancestry
• 93% of varying inherited traits are no more
common in people of one skin color than any
other
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Investigating Multifactorial Traits
• Empiric risk measures the likelihood that a trait
will recur based on incidence
• Incidence is the rate at which a certain event
occurs
• Prevalence is the proportion or number of
individuals who have a particular trait at a
specific time
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Investigating Multifactorial Traits
• Cleft lip is more likely
in a person who has a
relative with the
condition
Figure 7.5
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Investigating Multifactorial Traits
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Heritability (H)
• Estimates the proportion of the phenotypic
variation in a population due to genetic
differences
Figure 7.6
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Heritability (H)
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Heritability (H)
• Researchers use several statistical methods to
estimate heritability
• One way is to compare the proportion of people
sharing a trait to the proportion predicted to share
the trait
• Expected proportion is derived by knowing the
blood relationships of the individuals
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Coefficients of Relatedness
• Proportion of genes shared between two people
related in a certain way
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Tracing Relatives
Figure 7.7
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Adopted Individuals
• Similarities between adopted people and adopted
parents reflect mostly environmental influences
• Similarities between adoptees and their biological
parents reflect mostly genetic influences
• Information on both sets of parents can reveal
how heredity and the environment both contribute
to a trait
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Twins
• Twin studies have largely replaced adoption
methods
• Concordance: Measures the frequency of
expression of a trait in both members of
monozygotic (MZ) or dizygotic (DZ) twins
• Twins who differ in a trait are said to be
discordant
• For traits largely determined by genes,
concordance is higher for MZ than DZ twins
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Twins
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Separating Genetic and Environmental
Influences
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Dizygotic twins - Shared environment and 50% of
genes
Monozygotic twins - Identical genotype and shared
environment
Twins raised apart - Shared genotype but not
environment
Adopted individuals - Shared environment but not
genes
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Twins
Figure 7.8
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Single Nucleotide Polymorphisms
(SNP)
• Sites in a genome where the DNA base varies in
at least 1% of the population
• In these studies, SNPs span the genome, rather
than define a single gene
• SNP can be anywhere among our roughly 3.2
billion base pairs
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SNPs
Figure 7.9
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Genome-Wide Association Studies
• Older techniques search for known gene variants,
typically in only a few people
• Sequencing of the human genome and the
HapMap project (which identifies SNPs) have led
to a new tool
• Seek correlations between SNP patterns and
phenotypes in large groups of individuals
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• Genome-wide association studies seek SNPs that are
shared with much greater frequency among individuals
with the same trait than among others
Figure 7.11
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Step-wise Approach to Gene Discovery
Figure 7.12
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Study Designs
• Cohort study: Researchers follow a large group
of individuals over time and measure many
aspects of their health
• Case-control study: Pairs of individuals are
matched so that they share as many characteristics
as possible
• SNP differences are then associated with the
presence or absence of the disorder
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Study Designs
• Affected sibling pair strategy: Scans genomes of
siblings for SNPs shared by those with the
condition, but not by those who don’t have it
• Homozygosity mapping: Performed on families
that are consanguineous
• Children in this case are more likely to inherit two
copies of the mutation
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Limitations of Genome-Wide
Association Studies
• Include so many data points and so are prone to error
• Reveal associations between two types of
information, not causes
• Bias can be introduced in the way the patient
population is selected
• Accuracy is affected by complicating factors, such as
phenocopy and epistasis
• May miss extremely rare SNPs
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Body Weight
• Multifactorial trait that reflects energy balance
• About 30% of all adults in the US are obese, and
another 35% are overweight
• Scientific studies use a measurement called body
mass index (BMI)
• BMI = weight (kg)/height2 (m2)
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Body Mass Index (BMI)
Figure 7.14
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Body Weight
• Studies on adopted individuals and twins indicate
a heritability of 75% for obesity
• Lifestyle, including diet and exercise, are
environmental components impacting weight
• Genes influence hunger and metabolism
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Leptin and Associated Proteins
• Leptin - Protein hormone produced by fat cells
• Acts on the brain to decrease appetite
• Ghrelin - Peptide hormone produced in the
stomach
• Responds to hunger by increasing appetite
• Important for general weight regulation
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Leptin and Associated Proteins
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Examples:
Samoan Island of Naura: 2/3 obese 1/3 diabetic
Pima Indians:
Sierra Madre Mountains of
Mexico Population Vs
Southern Arizona Population
Low weight babies
full term:
Compensates for
starvation by metabolism
shift before birth.
Thrifty Gene Hypothesis
Gut Microbiome: Certain Bacteria increase efficiency
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Skin Pigmentation: 3 Polygenes
Gamete
s
ABC
ABc
AbC
Abc
aBC
aBc
abC
abc
ABC
6
5
5
4
5
4
4
3
ABc
5
4
4
3
4
3
3
2
AbC
5
4
4
3
4
3
3
2
Abc
4
3
3
2
3
2
2
1
aBC
5
4
4
3
4
3
3
2
aBc
4
3
3
2
3
2
2
1
abC
4
3
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2
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abc
3
2
2
1
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1
1
0
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1.07
3
2.5
Number
2
Male
1.5
Female
1
0.5
Male Av .508
Female Av .529
0
0.49 0.5 0.51 0.52 0.53 0.54 0.55 0.56 0.57 0.58
Ratio: Trunk : Height
2017
50
45
40
35
Number
30
25
20
15
10
5
0
Male
Female
Male Av .515
Female Av .539
0.49 0.5 0.51 0.52 0.53 0.54 0.55 0.56 0.57 0.58
Ratio: Trunk : Height
Summary 2017