Single Gene
Inheritance
(Mendelian
Genetics)
How to examine single traits
• ________________= crossing of two individuals that differ in a single given trait.
These parents are typically True Breeders.
• ______________= individuals that only produce offspring with the same traits,
thus their alleles are homozygous
• _________ Generation = (aka P1) the parents being crossed
• ______ Generation = (aka F1, F2, etc) the subsequent offspring of the P1
generation being crossed
• ________ = the offspring of the cross between two True Breeders, thus the F1 will
have different alleles.
Mendel’s Monohybrid Cross
Parental generation (P1) = Both are _______________
Filial generation (F1) = Are ___________, Not “true
breeders”
Filial generation (F2) = Result of Self-cross
½ true breeders
½ not true breeders
What Mendel Learned
_________________= when 2 different alleles for a
single trait, one allele is dominant over the recessive
allele
___________ = allele that is expressed when present in
one copy (masks the other allele)
___________ = allele whose expression is masked by
another allele (the dominant allele)
-Hybrids “hide” the expression of a trait.
-Tall plants could be TT or Tt
-Shows that in a hybrid (Tt) that the T (tall) is
expressed while the t (short) is hidden
Law of Segregation
During gamete production, 2 copies of each hereditary factor segregate so that
offspring acquire ______________________
4 main principles of the Law of Segregation
1. A gene can exist in more than one form (_____)
2. Organisms inherit ________for each trait
3. When gametes are made (meiosis) allele pairs separate so that each
cell has a ______________ for each trait
4. When 2 allele pairs are ________, one is dominant and the other is
recessive
Law of Segregation
• __________ = the allele combination of an
individual that causes a particular trait (ex. tall
plants could be (TT) or (Tt) & short plants would
be (tt)
• ____________ = the physical expression of a
gene’s trait (ex. tall or short plants)
• ____________ = the most common expression
of an allele combination in a population
• ____________ = an allele that differs from the
wild-type population (alters the phenotype)
v.
• ____________ = change in a protein encoding
gene that affects the phenotype
Following Segregating Genes
• ______________= diagram that maps out
possible genotypic/phenotypic outcomes of
different allele combinations
• _____________ = 2 identical alleles for a
particular trait (can be dominant or recessive)
• _____________ = 2 different alleles for a
particular trait (one is dominant & one is
recessive)
• Genotypic ratios 1 (TT) : 2 (Tt) : 1 (tt)
vs
• Phenotypic ratios 3 Tall ( TT, Tt, Tt) : 1 Short (tt)
Following Segregating Genes
____________ = Cross
individual with unknown
genotype with a
homozygous recessive
individual
Single gene inheritance is rare
• Pea plants “either or”
• Humans much more complex
• Genes interact with:
1. Other Genes
2. ______ that turns it on/off
3. ___________ alterations
4. ______________ influences
Following the inheritance of one gene
• ____________________________= Pattern a gene variant passes
from generation to generation
• Can be:
1. Dominant MOI
2. Recessive MOI
3. Autosomal MOI
4. Sex Linked MOI
5. Mitochondrial MOI
MOI - Autosomal Dominant
Criteria for Autosomal Dominant Traits
1. Affects both males and females & male to male
transmission is________
2. Males & females transmit with ______________
3. Does _____ skip a generation
4. Transmission ______ after generation where no
one is affected
Huntington’s Disease : Neurodegenerative,
symptoms in 20’s, death within 15 years, always fatal
MOI - Autosomal Recessive
Criteria for Autosomal Recessive traits
1. ________________can be affected
2. Affected males & females can transmit the trait unless the
trait causes death before reproductive age
3. ______ skip generations
4. Affected person’s parents are either ______________ or
have the trait
Cystic Fibrosis: 1950’s 10yo, 2007 37yo die of respiratory
infections
_____________: marriage between relatives increases
chances – Qatar, ½ of all marriages between 1st cousins
Following the inheritance of
more than one gene
Law of Independent Assortment
• When 2 or more
characteristics are
inherited, individual
hereditary factors assort
_______________ during
gamete production, giving
different traits an ______
opportunity of occurring
together.
Following 2 different genes
_______________=
2 different genes for 2
different traits
9:3:31
Product Rule
Predicts the chance that
parents with known
genotypes can produce
offspring of a particular
genotype
What is the probability
of offspring having the
genotype rryy if both
parents are RrYy
Chance of having rr = ___
Chance of having yy = __
______________
Using
probability
to track 3
traits
What is the
probability of
having a child
with bb, Hh, Ee
__________
Pedigree components
Beyond Mendel’s Laws
Lethal alleles
• An allele combination that causes death, usually denotes_________________
• Can cause death at any age (Tay-Sachs = age 3, Huntington’s = age 40+)
• May cause death before reproductive age, thus preventing passage to the ________________
• Can be dominant or recessive
- Homozygous recessive = Harlequin ichthyosis
- Homozygous dominant = Achondroplastic dwarfism
• Other forms of lethal alleles
1. ______________ = death only happens under certain conditions (Favism disease)
2. ______________ = cause death in some of the individuals with the genotype (hemophilia)
3. ______________ = combination of 2+ alleles leads to death, but mutation in only one does not
Multiple Alleles
• You have 2 alleles for any autosomal gene, one on each
homolog
• Each gene can exist in more than 2 ____________ in a
population
• Produces variations in phenotype, more alleles = more
phenotypes
• Example human ABO blood type
There are _____ alleles for blood type (IA, IB, i)
There are _____ possible genotypes for blood type
There are ______ possible phenotypes for blood type
Compound Heterozygote
• Person has 2 different alleles, each with a _______________
• Can sometimes predict the course of a disease:
Phenylketonuria (PKU) – lack enzyme to break down
phenylalanine, Depending on the allele and mutations can
be:
1. classic PKU – profound intellectual disability
2. moderate PKU – moderate intellectual disability
3. mild PKU – mild intellectual disability
4. asymptomatic PKU – body gets rid of phenylalanine
Different Dominance Relationships
1. ___________________ = one allele is
expressed, the other is masked
2. ____________________ = heterozygote has an
intermediate phenotype between the
homozygous dominant & homozygous
recessive forms
- (Ex. Familial hypercholesterolemia)
3. _____________ = different alleles are both
expressed in the heterozygote
- (ex. ABO blood group)
• Blood type is determined by pattern of
molecules on RBC
• A & B __________ (thus the AB bloodtype)
• A is dominant to O
• B is dominant to O
Epistasis
• When one gene ________the phenotype of an entirely different gene
• Is the interaction between __________ genes, not the alleles of the same gene
• The gene that affects expression of another gene is called the _____________
• The blocked gene is expressed normally, but the product of the modifier gene
_____________
• Example:
Spinal muscular atrophy vs plastin 3 gene
Penetrance
• All or non expression of a genotype
• _________ penetrance = allele combination that produces a phenotype in
everyone who inherits it (very rare)
- Ex. Huntington’s disease
• ___________ penetrance = some individuals do not express the phenotype,
usually described numerically
- If 80 of 100 people show the phenotype = 80% penetrance
- Ex. Mutation in BRAC1 & 2 genes
Expressivity
• The _________________ of the trait or mutation
• Varies in intensity among different people
• Ex. Polydactyly
How Penetrance & Expressivity work together
___ of the
individuals have the
_____ mutant
phenotype
___ of the
individuals have
_________ mutant
phenotypes
______ of the
individuals have
the ______
mutant
phenotype
______ of the
individuals have
_______ mutant
phenotype
Pleiotrophy
• A single gene disorder (mutation) that
causes several __________________
• Very hard to trace in families
• Ex. Porphyrias = porphyrins (heme
like)
Genetic Heterogenicity
• Mutation in different genes that produce
the __________________
• Occurs when
1. Genes encode enzymes that catalyze the
same ________________
2. Genes encode different proteins that are
part of the ____________
Ex. Osteogenesis Imperfecta vs child abuse
OI
xray
Normal
xray
Phenocopy
• An _______________ caused phenotype that appears to be inherited
genetically
• Occurs when:
1. Environmental factors produce symptoms that resemble those in
___________________
2. Environmental factors mimic __________________ by affecting certain
relatives
Ex. Thalidomide & phocomelia
Mitochondria
• Mitochondrial DNA (mtDNA) is
_____________ inherited
• Only contains 37 genes (24 RNA
molecules, 13 proteins)
• Mitochondrial myopathy
encephalopathy lactic acidosis
syndrome (MELAS)
• Powerful tool for science:
forensics, wars, historical records
Mitochondrial (continued)
• MOI
• _______________ = some
mitochondria have the mutation,
some do not
• ______________ = all
mitochondria are either wild-type
or mutant
Linkage
same
• The transmission of genes on the _______
chromosome
• These genes DO NOT:
1. Assort ___________________
2. Produce __________________
• Linkage is disrupted by __________
• This disruption is more likely between genes that have
________________ from each other
Multifactorial Traits
Genes & the environment mold traits
• Single gene : Mendelian inheritance
- one gene = one trait
Very rare (almost nonexistent in humans)
• Polygenic : trait due to more than one gene
Rare (most are also multifactorial)
• Multifactorial : trait determined by _____________& the ______________
- follow Mendel’s law (but harder to predict)
- can be single gene or polygenic • Most common
Polygenic traits are continuously varying
•
-
One loci
Quantitative trait loci (QTL)
Quantitative trait = “measurable trait”
Loci = “location”
Mapping genes that contribute to _______________
• Individual genes of a polygenic trait (how they contribute)
1. Follow Mendel’s law, but together do not make typical phenotypic ratios
2. All contribute to the __________
3. Are NOT dominant/recessive to each other
4. When plotted usually form _________
Multiple loci
Continuously Varying Multifactorial traits - Fingerprints
• ______ = always have the same throughout life (nobody’s are the same)
• Structure : Arches, Loops, Whorls = can have 1, 2 , or all 3
• How do we get them? Hint: Identical twins do not have the same
1. Genes = pattern types ARE inherited
2. Environment = _________________ so individual differences are not inherited
• Total Ridge Count & syndromes
(Men=145, Females=126)
# if whorls, loops, arches ___________
Klinefelter’s Syndrome_____________
lots of arches on 1st finger
Naegeli Syndrome _________________
Dermatoglyphics = scientific study of fingerprints
Continuously Varying Multifactorial traits - Height
1920
5’9”
6’5”
1997
5’9”
• How do we get our height
1. 70% Genetics – about 50 different genes suggested (localized
to chromosomes 7, 8, 20, X)
Don’t know why difference between males & females
2. 30% Environmental – availability of nutrients
• Genetic potential – developed vs non-developed
Continuously Varying Multifactorial traits – skin color
• How do we get our skin color
1. Genetics
• 100 different genes identified for skin, hair, iris
• Melanocytes  Melanosomes  Melanin
• Different combinations create different colors
2.
Environment (past)
• Melanin is a natural sunscreen
• UV strips away folic acid, but makes Vitamin D
• Migration of people required a delicate balance
Old ways of studying multifactorial traits
• Empiric risk
• Heritability
• Adoption studies
• Twin studies
New ways of studying multifactorial traits
• Genome wide association studies
Studying multifactorial traits – Empiric Risk (old)
• Empiric risk – probability that a trait will occur based upon its ________________
• Based on
1. _________ = rate at which a certain event occurs (# of new cases diagnosed per year in a
given population.
2. ___________ = # of individuals in a population who have a disorder at a specific time
• Is a population statistic based on observation, not a calculation
• Can be broad (ex. Ethnic group) or specific (families with CF)
• Increases with
1. _________ of affected family members
2. ___________ related you are to an affected family member
3. __________ of the disorder
Studying multifactorial traits – Heritability (old)
• Heritability – an estimate of the amount of __________________ that is
due to genes
• Different from empiric risk
1. Heritability ___ a calculation, empiric risk _____
2. Heritability focuses on _______, empiric risk considers genes +
environment
• Heritability changes as the environment changes
• Heritability equals 1 if a trait’s variability is completely ______
• Use the coefficient of relatedness to calculate = proportion of genes 2
related people share
Studying multifactorial traits
Twins
• Great tools, but differ in ______
• Monozygotic _________ vs. Dizygotic _________
• _____________ = % of pairs which both twins express trait
• University of Minnesota Twin Conference
Adoption studies
• Share _____________ with adopted parents, but not genes
• Share________ with biological parents, but not environment
• Denmark study on cause of Death
- biological parent died of infection, biological child 5x more likely
- adoptive parent died of cardiovascular disease, adopted child 3x more likely
Studying multifactorial traits – GWAS (new)
• Genome Wide Association Studies
• Older techniques looked for __________________ in a ____ people,
• GWAS looks for ___________________ in _______people for common
gene variants
• GWS look at observable traits like BP, weight, presence/absence of disease
• Limitations
1. Reveal _____________________
2. Sample population ___________ (clinics: only see affected, not those that
died)
3. Misses _______________
4. Can lead to _______________ (atherosclerosis – mutation or
infection/smoking/exercise/diet)