4 Extensions of Medelian inheritance
Mendelian inheritance= inheritance pattern that follows Mendel’s laws; involves the transmission of
eukaryotic genes that are located on the chromosomes found within the cell nucleus.
Obey 2 laws: law of segregation+ law of independent assortment.
Simple Mendelian inheritance= involves a simple (1 gene with 2 different alleles), dominant/ recessive
relationship that produces observed ratios in the offspring that readily obey Mendel’s laws.
4.1 Overview of simple inheritance patterns (fig 4.1)
Purpose of examining inheritance patterns:
To predict the outcome of crosses: 2 heterozygous organisms; not always offspring in a 3:1 phenotypic ratio.
To understand how the molecular gene expression can account for an individual’s phenotype .
Understanding the relationship between the molecular gene expression, function of the product
(protein/ RNA)+ trait in which the protein plays a role.
4.2 Dominant and recessive alleles
Recessive mutant alleles often cause a reduction in the amount or function of
the encoded proteins
Wild-type allele= prevalent allele in a natural population (found in >1% of the population).
Typically encodes a protein that is made in the proper amount+ functions normally.
Genetic polymorphism= 2/ more alleles occur in population.
Polymorphic genes: >1 wild-type allele (each allele is found at a frequency of 1% or higher).
Mutant allele= due to altering wild-type allele by mutation (rare in natural populations)-> associated with diseases.
Likely to decrease the amount/ the expression of a functional protein (mutated allele isn’t always defective!)
Recessive allele usually contains a mutation; causes a defect in the synthesis of a fully functional protein.
Often inherited in a recessive fashion; mutant phenotype visible when the individual has 2 of these alleles.
Recessive allele doesn’t affect the phenotype of the heterozygote; masked by a dominant allele.
2 possible explanations for the wild-type phenotype of the heterozygote:
1. 50% of the normal (functional) protein is enough to provide the wild-type phenotype (fig 4.2).
2. Heterozygote may produce more than 50% of the functional protein.
Increased expression of the normal gene (up-regulated); compensates defective allele’s lack of function.
Dominant mutant alleles usually exert their effects in one of three ways
3 mechanisms that account for most dominant mutant alleles (mutant allele dominant over a wild-type allele):
Gain-of-function mutation= changes a gene product so that it gains a new/ abnormal function.
Mutant gene may be overexpressed/ expressed in the wrong cell type.
Dominant-negative mutation= produces an altered gene product that acts antagonistically to the normal
gene product-> shows a dominant inheritance pattern.
Haploinsufficiency= individual only has 1 functional allele (+1 inactive allele); doesn’t produce normal
phenotype-> shows a dominant inheritance pattern-> e.g., polydactyly in humans.
Traits may skip a generation due to incomplete penetrance and vary in their
expressivity
Incomplete penetrance= allele that is expected to cause a particular phenotype doesn’t.
Polydactyly= autosomal dominant trait; affected individual has additional fingers/ toes.
Single copy sufficient to cause this condition.
Dominant allele doesn’t always ‘penetrate into’/ lead to the phenotype of the individual.
Some carry the allele but don’t express it phenotypically.
Measure of penetrance is described at the population level.
If 60% of heterozygotes carrying a dominant allele exhibit the trait allele; trait is 60% penetrant.
At individual level: trait is either present or not.
, Expressivity= degree to which a trait is expressed.
Polydactyly: individual extra digits hands+ feet (high expressivity) vs only on 1 foot (low expressivity).
Incomplete penetrance+ variable expressivity: range of phenotypes often due to:
Environmental influences
Modifier genes (alter the phenotypic effects of other genes)-> ‘genetic background’ of the individuals.
4.3 Environmental effects on gene expression
Norm of reaction= effects of environmental variation on an individual’s traits-> environmental factors can influence
the allele expression; influencing the phenotypes-> examples:
Temperature-sensitive allele= resulting phenotypes depends on the environmental temperature.
Artic fox: changes coat color summer (grayish brown) vs winter (white).
Humans with phenylketonuria (PKU): can't metabolize phenylalanine.
Standard diet (most protein-rich foods): mental impairment, underdevelopment teeth+ stinky urine.
Detected early+ restricted diet (no phenylalanine): remains symptom free (normal phenotype).
Humans can't synthesize vitamin C; due to a mutant GULO gene-> no problem as vitamin C is in our diet!
4.4 Incomplete dominance, overdominance, and
codominance
Incomplete dominance occurs when two alleles produce an intermediate
phenotype (fig 4.5)
Incomplete dominance= heterozygote that carries 2 different alleles exhibits a phenotype that is intermediate to
those of the corresponding homozygous individuals.
4 o’clock plant: P: CR x CW F1: all pink flowers (CRCW) F2: 1:2:1 phenotypic ratio (red: pink: white).
Not the 3:1 ratio observed in simple Mendelian inheritance.
In this case, 50% of the CR protein isn’t sufficient to produce the red phenotype.
50% functional protein can't accomplish the same level of pigment synthesis that 100% protein can.
Our judgement of dominance may depend on the level of examination (fig 4.6)
Trait dominant/ incompletely dominant: may depend on how closely the trait is examined.
Level of visual examination: R dominant to r.
Mendel visually concluded: RR and Rr round peas+ rr wrinkled peas.
Level of starch biosynthesis: R+ r alleles show incomplete dominance.
Microscopic examination reveals: heterozygote round seeds contain an intermediate number of starch
grains compared to homozygote round seeds intermediate amount of functional protein; not enough
to produce as many starch grains as the homozygote (has 2 copies of the R allele).
Overdominance occurs when heterozygotes have greater reproductive success
(fig 4.7)
Overdominance (heterozygote advantage)= heterozygote has greater reproductive success than either of the
corresponding homozygotes.
EXAMPLE OVERDOMINANCE: SICKLE CELL ANEMIA
Autosomal recessive disorder (on a non-sex chromosome).
Two alleles: HbA (normal hemoglobin)+ HbS (abnormal hemoglobin).
Affected individuals (HbSHbS) produce abnormal form of hemoglobin (hemoglobin S); red blood cells deform
into a sickle shape under conditions of low oxygen concentration-> 2 major consequences:
1. Sickling phenomenon greatly shortenes the life span of the red blood cells results in anemia.
2. Abnormal sickled cells clump partial/ complete blocks in capillary circulation.
Localized areas of oxygen depletion pain+ sometimes tissue and organ damage.
Affected individual tend to have a shorter life span than unaffected ones.
Mendelian inheritance= inheritance pattern that follows Mendel’s laws; involves the transmission of
eukaryotic genes that are located on the chromosomes found within the cell nucleus.
Obey 2 laws: law of segregation+ law of independent assortment.
Simple Mendelian inheritance= involves a simple (1 gene with 2 different alleles), dominant/ recessive
relationship that produces observed ratios in the offspring that readily obey Mendel’s laws.
4.1 Overview of simple inheritance patterns (fig 4.1)
Purpose of examining inheritance patterns:
To predict the outcome of crosses: 2 heterozygous organisms; not always offspring in a 3:1 phenotypic ratio.
To understand how the molecular gene expression can account for an individual’s phenotype .
Understanding the relationship between the molecular gene expression, function of the product
(protein/ RNA)+ trait in which the protein plays a role.
4.2 Dominant and recessive alleles
Recessive mutant alleles often cause a reduction in the amount or function of
the encoded proteins
Wild-type allele= prevalent allele in a natural population (found in >1% of the population).
Typically encodes a protein that is made in the proper amount+ functions normally.
Genetic polymorphism= 2/ more alleles occur in population.
Polymorphic genes: >1 wild-type allele (each allele is found at a frequency of 1% or higher).
Mutant allele= due to altering wild-type allele by mutation (rare in natural populations)-> associated with diseases.
Likely to decrease the amount/ the expression of a functional protein (mutated allele isn’t always defective!)
Recessive allele usually contains a mutation; causes a defect in the synthesis of a fully functional protein.
Often inherited in a recessive fashion; mutant phenotype visible when the individual has 2 of these alleles.
Recessive allele doesn’t affect the phenotype of the heterozygote; masked by a dominant allele.
2 possible explanations for the wild-type phenotype of the heterozygote:
1. 50% of the normal (functional) protein is enough to provide the wild-type phenotype (fig 4.2).
2. Heterozygote may produce more than 50% of the functional protein.
Increased expression of the normal gene (up-regulated); compensates defective allele’s lack of function.
Dominant mutant alleles usually exert their effects in one of three ways
3 mechanisms that account for most dominant mutant alleles (mutant allele dominant over a wild-type allele):
Gain-of-function mutation= changes a gene product so that it gains a new/ abnormal function.
Mutant gene may be overexpressed/ expressed in the wrong cell type.
Dominant-negative mutation= produces an altered gene product that acts antagonistically to the normal
gene product-> shows a dominant inheritance pattern.
Haploinsufficiency= individual only has 1 functional allele (+1 inactive allele); doesn’t produce normal
phenotype-> shows a dominant inheritance pattern-> e.g., polydactyly in humans.
Traits may skip a generation due to incomplete penetrance and vary in their
expressivity
Incomplete penetrance= allele that is expected to cause a particular phenotype doesn’t.
Polydactyly= autosomal dominant trait; affected individual has additional fingers/ toes.
Single copy sufficient to cause this condition.
Dominant allele doesn’t always ‘penetrate into’/ lead to the phenotype of the individual.
Some carry the allele but don’t express it phenotypically.
Measure of penetrance is described at the population level.
If 60% of heterozygotes carrying a dominant allele exhibit the trait allele; trait is 60% penetrant.
At individual level: trait is either present or not.
, Expressivity= degree to which a trait is expressed.
Polydactyly: individual extra digits hands+ feet (high expressivity) vs only on 1 foot (low expressivity).
Incomplete penetrance+ variable expressivity: range of phenotypes often due to:
Environmental influences
Modifier genes (alter the phenotypic effects of other genes)-> ‘genetic background’ of the individuals.
4.3 Environmental effects on gene expression
Norm of reaction= effects of environmental variation on an individual’s traits-> environmental factors can influence
the allele expression; influencing the phenotypes-> examples:
Temperature-sensitive allele= resulting phenotypes depends on the environmental temperature.
Artic fox: changes coat color summer (grayish brown) vs winter (white).
Humans with phenylketonuria (PKU): can't metabolize phenylalanine.
Standard diet (most protein-rich foods): mental impairment, underdevelopment teeth+ stinky urine.
Detected early+ restricted diet (no phenylalanine): remains symptom free (normal phenotype).
Humans can't synthesize vitamin C; due to a mutant GULO gene-> no problem as vitamin C is in our diet!
4.4 Incomplete dominance, overdominance, and
codominance
Incomplete dominance occurs when two alleles produce an intermediate
phenotype (fig 4.5)
Incomplete dominance= heterozygote that carries 2 different alleles exhibits a phenotype that is intermediate to
those of the corresponding homozygous individuals.
4 o’clock plant: P: CR x CW F1: all pink flowers (CRCW) F2: 1:2:1 phenotypic ratio (red: pink: white).
Not the 3:1 ratio observed in simple Mendelian inheritance.
In this case, 50% of the CR protein isn’t sufficient to produce the red phenotype.
50% functional protein can't accomplish the same level of pigment synthesis that 100% protein can.
Our judgement of dominance may depend on the level of examination (fig 4.6)
Trait dominant/ incompletely dominant: may depend on how closely the trait is examined.
Level of visual examination: R dominant to r.
Mendel visually concluded: RR and Rr round peas+ rr wrinkled peas.
Level of starch biosynthesis: R+ r alleles show incomplete dominance.
Microscopic examination reveals: heterozygote round seeds contain an intermediate number of starch
grains compared to homozygote round seeds intermediate amount of functional protein; not enough
to produce as many starch grains as the homozygote (has 2 copies of the R allele).
Overdominance occurs when heterozygotes have greater reproductive success
(fig 4.7)
Overdominance (heterozygote advantage)= heterozygote has greater reproductive success than either of the
corresponding homozygotes.
EXAMPLE OVERDOMINANCE: SICKLE CELL ANEMIA
Autosomal recessive disorder (on a non-sex chromosome).
Two alleles: HbA (normal hemoglobin)+ HbS (abnormal hemoglobin).
Affected individuals (HbSHbS) produce abnormal form of hemoglobin (hemoglobin S); red blood cells deform
into a sickle shape under conditions of low oxygen concentration-> 2 major consequences:
1. Sickling phenomenon greatly shortenes the life span of the red blood cells results in anemia.
2. Abnormal sickled cells clump partial/ complete blocks in capillary circulation.
Localized areas of oxygen depletion pain+ sometimes tissue and organ damage.
Affected individual tend to have a shorter life span than unaffected ones.
