Revision as of 11:41, 3 August 2018

Modern genetics can be divided into four main fields: quantitative genetics, classical genetics, population genetics, and molecular genetics. The following sections are a brief introduction to each of these fields, not that they are not integrated with each other and with other fields within and outside of biology. The concept of heritability is a good place to start in quantitative genetics. The connection between genotype and phenotype is used in classical genetics. Hardy-Weinberg genotype proportions introduce population genetics. And the flow of information from DNA to RNA to protein is mentioned in molecular genetics. Finally, the fields of statistics and genetics are closely connected, especially in a historical sense, and this is introduced with binomial probabilities. 

Quantitative Genetics Introduction

A species is characterized by a range of traits such as height, length, pigmentation, weight, and growth rates. The genetic component of these traits can be quantified. These traits are called phenotypes and the amount of variation in the trait that is determined by genetic differences is called heritability. A classical example is human height. Stature is partially influenced by genetic variation and partially influenced by environmental factors such as health and nutrition.  We tend to be more similar in height to our own parents than to unrelated people, but we cannot predict someone's height with perfect accuracy from their parents' height. Another overt example in humans is skin color. There is genetic variation that influences skin pigmentation. Again, children tend to be more similar to their parents in comparison to randomly selected people; however, there are also clear non-genetic environmental influences that influence skin color, such as exposure to ultraviolet light.

Let's switch gears and talk about something with no heritabilty to illustrate. We can roll two six-sided dice in a game of craps and add up the total from two (snake eyes) to 12 (boxcars). If we have fair dice the outcome of the first roll has no influence on the outcome of the second roll. The outcomes are only a result of physics: the speed, rotation, air drag, starting orientation, and friction with a surface. Dice have zero heritability (influence from previous rolls) and are only influenced by environmental effects. If we plotted the results from a first and second roll we do not expect a significant correlation in the sum of two dice.

A counter example is eye color in humans. Iris pigmentation due to the amount of melanin is almost completely explained by genetic variation inherited from our parents and has essentially no influence from the environment. If we scored the eye color of a large number of parents and offspring we expect a significant correlation because eye color is heritable and due to these genetic effects.

There are a wide range of traits in various species that have a range of heritability. Domesticated plant varieties and animal breeds are good examples. Phenotype variation selected by humans has increased the underlying genetic variation. Breeds have certain sets of unique traits because of a high heritability of these traits. 

However, keep in mind that not all variation is heritable and due to genetic variation. American redstarts have variation in some of the feathers, from lighter yellow to darker orange-red, that is due at least in part to the availability of carotenoids in their diet and may indicate relative nutrition levels (Reudink et al., 2014).  

Later I will write about how to quantify heritability, different types of heritability, how heritability can be used to make predictions in artificial selection experiments and some additional related topics.

Classical Genetics Introduction

Many species, such as humans and fruit flies, have two copies of most genes in their genome. There are tens of thousands of these genes across the genome. A gene can have different forms that alter the genes function. These forms of a gene are called alleles. Many tools come in different forms and this affects how they perform at different tasks. Some spoons are better for transferring liquid and some are designed to strain liquid. Some blades are used to carve wood and some are used to chop wood. These different forms can be thought of as alleles of a tool. Different tools are used to carry out different types of work; these tools can be thought of as genes which carry out different jobs within a cell. The collection of all the tools a family has can be metaphorically thought of as a genome. We often have spares or more than one copy of a single tool. In a similar way our genome has two copies of most genes. If one copy isn't working correctly there is usually a backup copy to carry out the function anyway. 

Phenotypes are traits that are observed that derive from, at least in part, a genetic basis. It is important later on to remember that phenotypes are defined by humans based on what we can observe. Our height, the color of a tomato, the coat color of a dog are all phenotypes. The two alleles of a gene are together called a genotype. If the two alleles are the same this is a homozygote. If an individuals has two different alleles of a gene they are a heterozygote. There is a link between the genotype and the phenotype of an individual but this depends on the type of dominance of the phenotype and the relationship between the phenotype and the alleles. 

A commonly encountered form of albinism in mammals is due to mutations at the albino gene (also called the c locus, locus is a synonym for gene in genetics, or the Tyr locus, named after the enzyme Tyrosinase  produced by the gene). In classical genetics the common allele of the gene is called the wildtype allele and is symbolized by a capital letter C. An inactive mutant allele of the gene, that does not produce Tyrosinase, is symbolized by a lower case c. There are three possible genotypes that arise from these two alleles: CC, Cc, cc. Having one copy of the functional allele produces a sufficient amount of the Tyrosinase enzyme to have a wildtype coat color. So, both the CC homozygote and Cc heterozygote genotypes result in individuals with a wildtype brown coat color. Individuals with a cc genotype do not produce any Tyrosinase and have the recessive albino coat color.

The actor Peter Dinklage has achondroplasia which results in shorter limbs; a condition known as achondroplastic dwarfism. This is due to a mutation in the FGFR3 gene that causes an arginine amino acid to replace a glycine at amino acid 380 in the assembled enzyme. The mutation results on an overly active form of the protein and disrupts cartilage formation needed for the development of long limb bones.  In this case the mutant allele (FGFR3[Gly380Arg]) results in a dominant phenotype; Peter Dinklage is heterozygous with a  FGFR3[Gly380Arg]/FGFR3[+] genotype (here + indicates the non-mutant allele) and has only one copy of the disrupted allele. Homozygous individuals with FGFR3[Gly380Arg]/ FGFR3[Gly380Arg] genotypes do not survive early development. The same set of alleles can result in a range of phenotypes with a range of dominance.  FGFR3[+] / FGFR3[+]  homozygotes are expected to have regular stature. FGFR3[Gly380Arg]/FGFR3[+] have shortened limbs, a dominant phenotype. FGFR3[Gly380Arg]/ FGFR3[Gly380Arg] homozygotes do not survive, a recessive lethal phenotype. 

The heterozygotes are the key to determining which phenotype is dominant. In the case of albinism Cc heterozygotes have brown fur so this is the dominant phenotype; a phenotype that is also shared with CC homozygotes. In the case of achondroplasia FGFR3[Gly380Arg]/FGFR3[+] heterozygotes have shortened limbs so this is a dominant phenotype and in this case the phenotype is not shared with FGFR3[+] / FGFR3[+] homozygotes.

The examples given here are cases of simple dominance where one phenotype is fully dominant or recessive to the other. There are a range of exceptions to this that will be discussed later. There are also different conventions used in naming and representing genes, alleles, and phenotypes. Two types have been used here with capital and lower case letters and designating the allele in brackets after the gene symbol (and using a + to indicate an non-mutant or wildtype allele). This will also be discussed more later on.

Population Genetics Introduction

Molecular Genetics Introduction

Genetics and Statistics Introduction

Glossary

Allele

Dominance

Environmental effects

Gene

Genetic effects

Genome

Genotype

Heritability

Heterozygote

Homozygote

Locus

Mutation

Phenotype

Wildtype

References

E. H. Hanson. HFE Gene and Hereditary Hemochromatosis: A HuGE Review. American Journal of Epidemiology 154, 193–206 Oxford University Press (OUP), 2001. Link

Matthew W. Reudink, Ann E. McKellar, Kristen L. D. Marini, Sarah L. McArthur, Peter P. Marra, Laurene M. Ratcliffe. Inter-annual variation in American redstart (Setophaga ruticilla) plumage colour is associated with rainfall and temperature during moult: an 11-year study. Oecologia 178, 161–173 Springer Nature, 2014. Link

Appendix