04: Extensions on Mendelian Inheritance

Two laws that govern Mendelian inheritance

Law of segregation, law of independent assortment

Genetic relationship described by simple Mendelian inheritance

A single gene with alleles that display a simple dominant or recessive relationship

Wild type allele

Type of allele most present in the population

Mutant allele

Any change that happens to the wild type allele

Why do heterozygotes with simple dominant/recessive alleles only display dominant characteristics

The recessive is often a loss of function. The singular dominant allele can either produce the expected phenotype sufficiently with only 50% of the coded protein, or the allele can be upregulated to compensate for the nonfunctioning recessive allele

Gain of function dominant mutation

Dominant mutant gene gains a new or abnormal function

Dominant negative mutation

The mutant protein acts antagonistically to the normal protein

Haploinsufficiency dominant mutation

The mutant allele is loss of function, and in a heterozygote the other wild type allele doesn’t make enough product to give the wild type phenotype

Incomplete penetrance

The dominant allele doesn’t always influence the phenotype of the heterozygote. The genotype is there, the phenotype might not always be exhibited

Example of incomplete penetrance

Polydactyly

If a trait is 45% penetrant for a given generation, what does that mean

45% of heterozygotes carrying the dominant allele exhibit the trait

Expressivity

The degree to which a trait is expressed (ex: having one v multiple extra digits)

Factors that influence the expressivity of genes that are incompletely penetrant

• Environment: greatest impact during development, but not exclusively so

• Modifier genes

Norm of reaction

How the environment affects a trait

Incomplete dominance

Heterozygote phenotype is a blend of both homozygote phenotypes

Why is the categorization of complete v incomplete dominance dependent on perspective

Macroscopically things can look black and white (round or wrinkled), but microscopically there can be a scale (lots of starch, medium starch, very little starch)

Overdominance

The heterozygote has greater reproductive success than either of the homozygotes; the homozygous dominant has a weakness because of only having dominant allele expression

Heterozygote advantage

The heterozygote is better suited for survival than homozygotes; characteristic of overdominance

Example of overdominance

Sickle cell disease (autosomal recessive disorder). Affected RBCs are resistant to malaria, but have lowered Hb function. Homozygous dominant RBCs have perfect Hb, but are totally susceptible to malaria. The heterozygote has mostly normal Hb, and is resistant to malaria without having sickle cell

Explanations for the evolutionary development of overdominance and the heterozygote advantage

• Heterozygosity bestows disease resistance

• Heterozygosity results in the formation of two types of proteins that can form an additional, better functioning homodimer than the single homodimer of either homozygote

• Heterozygotes produce proteins and enzymes that function in a broader environmental range

Codominance

Both dominant alleles in a heterozygote are expressed

What biological reality facilitates codominance

A gene with multiple types of dominant alleles influencing function

Example of codominance

Blood type

Sex-linked gene

Gene is present on a sex chromosome, and thus inheritance can be dependent on the sex of the offspring and which parent is affected or a carrier

Pseudoautosomal inheritance

Gene is present on a sex chromosome, but it is on a conserved region that is present in regions on both X and Y that are needed for chromosome pairing. So the inheritance pattern is functionally that of an autosomal gene

Sex-influenced inheritance

The way a gene is expressed (dom v rec) is influenced by the sex of the organism. These genes are autosomal, and the sex-influence is only present in heterozygotes

Sex-limited inheritance

Gene can be present in both M and F, but is only expressed in one of the two sexes

Example of sex-limited inheritance

Plumage color in male birds

Key factors in sex-limited inheritance

Sex hormones and developmental pathways

Lethal allele

Allele has the potential to cause organismal death; this is usually because the modified gene is an essential gene

Why do the inheritance patterns of lethal alleles not seem to follow Mendelian inheritance

The early embryonic death of affected individuals causes holes in data

Essential gene

A gene that is absolutely required for survival, and the absence of its protein leads to a lethal phenotype

Conditional lethal allele

Death can be avoided or induced in certain environmental conditions, often temperature

Semilethal alleles

Allele kills some individuals but not all; depends on environment and other gene interactions

Pleiotrophy

A gene that produces multiple effects

Explanations for pleiotrophy

• Gene product is part of multiple pathways

• Gene is expressed in different cell types

• Gene is expressed in different developmental stages

Gene interactions

Two or more different genes affect a single trait

Complementation

For a given collection of genes, each is comprised of a recessive and wild type allele. The recessive alleles are in different genes.

Epistasis

If either gene is homozygous recessive, there will be a loss of function/recessive phenotype; the homozygous recessive gene can mask the phenotypic effects of another gene, no matter the allele composition

In what situation does epistasis arise

When two or more different proteins participate in a common cellular function or pathway

Gene modifier affect

The expressed phenotype is dependent on the genes present in the genotype for interaction

Gene redundancy

Multiple copies of a gene are present in the genome

Advantage provided by gene redundancy

Loss of function alleles in one location has no affect on the phenotype

Paralogous genes

Genes with different functions, but are related because at one point they were identical, duplicated genes

Advantage provided by paralogs

If one gene copy disappears, the function of the other may be able to compensate if upregulated and overcome the defect