Mendelian inheritance
Hereditary
Figure 1. Humans have 23 pairs of chromosomes, 22 pairs of autosomes, and one pair of sex chromosomes. Because there are both X and Y present, this individual is a male.
As humans, we have two copies of chromosomes containing many genes. We inherit one set of chromosomes from our father and one set from our mother. In total, there are 46 chromosomes in each of our cells: 23 from the father and 23 from the mother. Chromosomes 1–22 are referred to as autosomes and the last chromosome pair (X or Y) is referred to as sex chromosomes. Chromosome 1 is the largest chromosome containing the most genes and is the longest chromosome in base pairs. Due to alternative splicing and the number of noncoding DNA, the number of genes located in a chromosome is not always proportional to the length of the chromosome. Figure 1 illustrates the 23 pairs of human chromosomes.
Allele
Allele is a number of alternative forms that a gene can have. Because we have two pairs of chromosomes, our genes have two alleles. The sex chromosomes are slightly different because males only have one X chromosome and one Y chromosome; therefore, genes that are located in these two chromosomes have only one allele.
As written above, a gene can have two alleles. If both alleles are the same, it is said to be homozygous; otherwise it is said to be heterozyous. Let’s consider an example of hair color; allele a is responsible to produce blond hair color, while allele A is responsible to produce dark hair color. Individuals with genotype aa or AA are homozygous while individuals with genotype aA or Aa are heterozygous.
An allele is dominant if it determines the phenotypic outcome. For example, an individual with genotype aA has dark hair color, which means that allele A is dominant over allele a. Because the outcome of genotype aA is the same as the outcome of genotype AA that is homozygous for dark hair color, only individuals with genotype aa have blond hair color. We normally denote the dominant allele as capital letters and the recessive allele as small letters.
| Genotypes | Phenotypes | |
|---|---|---|
| AA | Dark hair | |
| Aa | Dark hair | |
| aA | Dark hair | |
| aa | Blond hair |
Many genes are involved in determining the phenotype, for example, hair color is determined by at least two genes: Eumelanin that produces the brown–black color and pheomelanin that predominates in red hair. Blond hair contains low levels of both pigments. In addition, more than one gene determines hair color; however, the expression level of these genes also plays a significant role. The higher the expression level, the higher the pigment levels.
Not all alleles have complete penetrance, as shown in the above mentioned example. Some alleles have incomplete penetrance, meaning that even though the individual has a certain genotype, this individual does not show the phenotype. For example, if allele A has incomplete penetrance, most people with genotype AA will have dark hair; however, some people having exactly the same genotype as AA have lighter hair.
Let’s consider an example of breast cancer. BRCA1/2 are highly associated with breast cancer. Many people carrying the mutation in their BRCA1/2 ended up developing breast cancer; however, not all of them developed breast cancer. A number of people are positive for BRCA1/2 mutation and do not develop breast cancer. This is because BRCA1/2 have an incomplete penetrance. The penetrance level can be difficult to determine because it can be modified by many factors such as age, environmental factors, other genes (polygenic), and epigenetic regulation.