Next Lesson - Gene Expression
Core
Our genotype, put simply, is the sum total of all our genes, encoded by DNA. Our phenotype is the physical manifestation of our genotype via proteins. For example, the human blood types are encoded by the ABO gene found on chromosome 9 (genotype). When translated the gene produces glycoproteins on the surface of red blood cells (phenotype).
It is important to note that the environment has an important effect on our phenotype. For example, Familial Adenomatous Polyposis genotypically predisposes someone to developing bowel cancer, but additional genetic damage influenced by environmental factors is required for cancer to develop. Similarly, the BRCA1 gene greatly increases a woman's lifetime risk of developing breast cancer to around 65-85%. However, as this risk is not 100% (that is, BRCA1 does not always lead to cancer), non-genetic factors must also be involved.
Each human has 25,000 genes, with two copies of each gene. The two copies of a gene may be the same or through random mutation may be ever so slightly different. Variants of the same gene are known as an allele. As we inherit one half of our genetic information from our mother, and one half from our father we inherit two unique sets of genes, and for a given gene we may inherit different alleles.
For a particular gene, an individual can be described as homozygous (both the allele from the mother and the father are the same) or heterozygous (both alleles are different). For the third category, hemizygous (only one allele of a gene is present on the x chromosome), it is important to understand that only males can be hemizygous, as they only have one x chromosome. Females cannot have a single copy of an allele for an X chromosome as they have two X chromosomes.
In a heterozygote, the dominant allele determines the phenotype, and the non-dominant allele does not determine the phenotype and is called recessive.
In some cases, for example the ABO gene, it is possible for two different dominant alleles in a heterozygote to exert an effect on the phenotype; this is known as co-dominance.
Figure: Blood Group Transfusion Table
SimpleMed original by Dr. Joshua Sturgeon
Please note, in reality a protein known as Rhesus Factor also plays a role in determining a person’s blood type (a person can be Rhesus Factor positive (+) or negative (-)), but this is beyond the scope of this article (see our haematology section). Just appreciate that blood group O- is known as the ‘universal donor’ as it is safe to transfuse into any patient, so is used in an acute situation where the patient’s blood group is unknown.
There are three alleles of the ABO gene: IA, IB, and IO. IA is dominant over IO. IB is also dominant over IO. However, neither allele IA or IB is dominant over the other, they are co-dominant. This co-dominance allows us to have the blood type AB. IO is the only allele of the ABO gene which is recessive.
Figure: Possible Genotypes for Blood Groups
SimpleMed original by Dr. Joshua Sturgeon
Figure: Pedigree Key
SimpleMed original by Dr. Joshua Sturgeon
Pedigrees are drawn using the symbols shown above. Each generation is placed on a separate line, each of which is numbered with a roman numeral. When drawing a generation of offspring, it is convention to have the oldest offspring on the left hand side. Within a generation, each individual is numbered from left to right. An example on how to interpret a pedigree chart is shown below.
Figure: Example Pedigree Chart. All members of generations I and II are deceased. The relations of III.17 are: wife III.18, parents II.1 and II.2, a sister III.3, and a niece IV.1. III.17 is genetically unrelated to III.4 and III.5, and to III.13 and III.14, and is therefore genetically unrelated to their respective offspring.
SimpleMed original by Dr. Joshua Sturgeon
Being able to interpret or even draw a pedigree chart from a given family history is a useful skill to have. An understanding of determining an inheritance pattern of an unknown disease from a pedigree chart is crucial.
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