Most genes are actually multifactorial.
Human height is an example of a multifactorial trait. Genes are present that encode for height, but an adequate diet is needed to reach that height. Malnutrition in early childhood can have an effect not only on height but also on neurological development as well as other biological systems. Accidents at any stage of life can also alter an individual’s phenotype. Multifactorial traits tend to follow Mendelian inheritance patterns, but the phenotypic results are difficult to predict due to the influence of the environment. Polygenic and multifactorial traits are discussed in greater detail in Chapter 4.
8. Epistasis
When one gene masks the effect of another unrelated gene it defies normal Mendelian inheritance patterns. Epistasis refers to the interaction of different genes, not between alleles of the same gene. A simplified example of epistasis in humans is that of the curly hair gene and the baldness gene. Although the curly hair gene is still expressed, it cannot have any effect on the phenotype of a bald individual.
A large number of proteins encoded by genes are involved in metabolic pathways. The absence of one step within the pathway will alter the outcome of the whole pathway. In epistasis, the remaining proteins needed to complete the pathway are present but are unable to interact in the pathway due to the ‘missing step’.
The Bombay phenotype within the ABO blood grouping in humans is also an example of epistasis. ABO blood groups are due to the presence of A and/or B antigens on the surface of red blood cells. The A and B antigens are attached to the cell surface by proteins that are embedded in the cell membrane. The A and B antigen is encoded for by one gene and the protein attachments are encoded for by a different gene. If an individual does not have an effective gene to encode for the protein attachments, then the A and B antigens have no means of attaching to the cell surface. This individual would then display a blood group O phenotype, even though the genotype might be AB.
9. Pleiotropy
Pleiotropy is the expression of several different phenotypes by a single allele. Most single genes affect more than one observable trait. Pleiotropy occurs in genes which encode for a single protein that has more than one function within the body. Genetic disorders involving a pleiotropic gene are difficult to detect within families, as different members of the same family may display different symptoms. Marfan syndrome (see Chapter 7) is an example of a human condition arising from a pleiotropic gene, in that members of the same family can display different phenotypic traits arising from the same gene.
| ACTIVITY 2.5 |
a. Benign epidermolysis bullosa is a condition that arises from an abnormal gene that encodes for collagen. The effect of this faulty gene results in the loss of skin and hair and in abnormal nails and teeth. Which of the following exceptions to Mendelian inheritance is this an example of: sex-related inheritance, genomic imprinting or pleiotropy?
b. One form of blindness is the autosomal dominant retinitis pigmentosa. The faulty gene that causes this type of blindness is incompletely penetrant. What do you understand by this statement?
Geneticists have identified thousands of genes that can lead to different traits, conditions and diseases. As more are discovered it is becoming clear that the ‘exceptions to the rules’ identified here are relatively common. However, a large proportion of traits are inherited in the Mendelian fashion.
| SUMMARY |
• Gregor Mendel, the father of genetics, outlined the four principles of inheritance. The principles of unit inheritance, dominance, segregation and independent assortment form the basis of Mendelian genetics.
• The principle of unit inheritance involves the transmission of hereditary units called genes. Genes are made up of two alleles, inherited from both parents.
• The principle of dominance involves the action of individual alleles within a gene, in that they are either dominant (will be expressed) or recessive. Recessive alleles are only expressed if both alleles are in a recessive form (or by the absence of a dominant allele).
• The principle of segregation refers to the separation of allelic pairs during meiosis. Allelic pairs are restored again at fertilisation.
• The principle of independent assortment concerns the inheritance patterns of two different genes. Alleles and genes resort independently from each other.
• An individual’s genotype refers to their genetic make up and their phenotype refers to the outward appearance or the measurable effect of that gene.
• The term homozygous refers to two alleles that carry the same DNA in the same gene and heterozygous refers to different alleles within the same gene.
• There are exceptions to the Mendelian principles that include:
♦ mitochondrial inheritance – maternal inheritance only;
♦ penetrance – not all dominant genes are expressed;
♦ genomic imprinting – some alleles may be silenced;
♦ sex-related effects – may be sex-limited or sex-influenced;
♦ mutations – DNA alterations can occur by chance as well as being inherited;
♦ genetic linkage – alleles that are positioned closely together on the same chromosome have a higher chance of being inherited together;
♦ polygenic and multifactorial traits – more common than single gene traits and may be influenced by the environment;
♦ epistasis – unrelated genes can mask the effect of a gene;
♦ pleiotropy – one single gene can result in the expression of different phenotypes, as one protein may have more than one function.
FURTHER READING
Cummings, M.R. (2008) Human heredity: Principles and issues. USA: Brooks Cole, International edition.
This is a well-written text, which has a good chapter on the transmission of genes from generation to generation (pages 44–69).
Griffiths, A.J.F., Gelbart, W.M., Lewontin, R.C. and Miller, J.H. (2002) Modern genetic analysis: Integrating genes and genomes. Palgrave:Hampshire, W.H. Freeman and Company.
Despite this text not being specifically about human genetics, it still has some very relevant material.
A good internet resource is Biology Online, which outlines Mendelian principles:
www.biology-online.org/2/1_meiosis.htm
Further information on the conditions mentioned in this chapter can be found on the Online Mendelian Inheritance in Man website:
www.ncbi.nlm.nih.gov/omim
Different genetic conditions are allocated a reference number on this site:
• Benign epidermolysis bullosa can be found as #226650.
• Autosomal dominant retinitis pigmentosa is referenced as #268000.
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