Figure 3.23: Statue of Mendel located at the Mendel Museum, located at Masaryk University in Brno, Czech Republic. Credit: Mendel´s statue by Coeli has been designated to the public domain (CC0).
Gregor Johann Mendel (1822–1884) is often described as the “Father of Genetics.” Mendel was a monk who conducted pea plant breeding experiments in a monastery located in the present-day Czech Republic (Figure 3.23). After several years of experiments, Mendel presented his work to a local scientific community in 1865 and published his findings the following year. Although his meticulous effort was notable, the importance of his work was not recognized for another 35 years. One reason for this delay in recognition is that his findings did not agree with the predominant scientific viewpoints on inheritance at the time. For example, it was believed that parental physical traits “blended” together and offspring inherited an intermediate form of that trait. In contrast, Mendel showed that certain pea plant physical traits (e.g., flower color) were passed down separately to the next generation in a statistically predictable manner. Mendel also observed that some parental traits disappeared in offspring but then reappeared in later generations. He explained this occurrence by introducing the concept of “dominant” and “recessive” traits. Mendel established a few fundamental laws of inheritance, and this section reviews some of these concepts. Moreover, the study of traits and diseases that are controlled by a single gene is commonly referred to as Mendelian genetics.
Figure 3.24: Various phenotypic characteristics of pea plants resulting from different genotypes. Credit: Mendels peas by Mariana Ruiz LadyofHats has been designated to the public domain (CC0 1.0).
The physical appearance of a trait is called an organism’s phenotype. Figure 3.24 shows pea plant (Pisum sativum) phenotypes that were studied by Mendel, and in each of these cases the physical traits are controlled by a single gene. In the case of Mendelian genetics, a phenotype is determined by an organism’s genotype. A genotype consists of two gene copies, wherein one copy was inherited from each parent. Gene copies are also known as alleles (Figure 3.25), which means they are found in the same gene location on homologous chromosomes. Alleles have a nonidentical DNA sequence, which means their phenotypic effect can be different. In other words, although alleles code for the same trait, different phenotypes can be produced depending on which two alleles (i.e., genotypes) an organism possesses. For example, Mendel’s pea plants all have flowers, but their flower color can be purple or white. Flower color is therefore dependent upon which two color alleles are present in a genotype.
Figure 3.25: Homozygous refers to having the same alleles (e.g. two capital Bs or two lowercase bs). Heterozygous refers to having two different alleles (e.g. one capital B and one lowercase b). Credit: Homozygous by NIH National Human Genome Research Institute is in the public domain.
A Punnett square is a diagram that can help visualize Mendelian inheritance patterns. For instance, when parents of known genotypes mate, a Punnett square can help predict the ratio of Mendelian genotypes and phenotypes that their offspring would possess. When discussing genotype, biologists use upper and lower case letters to denote the different allele copies. Figure 3.26 is a Punnett square that includes two heterozygous parents for flower color (Bb). A heterozygous genotype means there are two different alleles for the same gene. Therefore, a pea plant that is heterozygous for flower color has one purple allele and one white allele. When an organism is homozygous for a specific trait, it means their genotype consists of two copies of the same allele. Using the Punnett square example, the two heterozygous pea plant parents can produce offspring with two different homozygous genotypes (BB or bb) or offspring that are heterozygous (Bb).
A pea plant with purple flowers could be heterozygous (Bb) or homozygous (BB). This is because the purple color allele (B) is dominant to the white color allele (b), and therefore it only needs one copy of that allele to phenotypically express purple flowers. Because the white flower allele is recessive, a pea plant must be homozygous for the recessive allele in order to have a white color phenotype (bb). As seen by the Punnett square example (Figure 3.26), three of four offspring will have purple flowers and the other one will have white flowers.
The Law of Segregation was introduced by Mendel to explain why we can predict the ratio of genotypes and phenotypes in offspring. As discussed previously, a parent will have two alleles for a certain gene (with each copy on a different homologous chromosome). The Law of Segregation states that the two copies will be segregated from each other and will each be distributed to their own gamete. We now know that the process where that occurs is meiosis.
Offspring are the products of two gametes combining, which means the offspring inherits one allele from each gamete for most genes. When multiple offspring are produced (like with pea plant breeding), the predicted phenotype ratios are more clearly observed. The pea plants Mendel studied provide a simplistic model to understand single-gene genetics. While many traits anthropologists are interested in have a more complicated inheritance (e.g., are informed by many genes), there are a few known Mendelian traits in humans. Additionally, some human diseases also follow a Mendelian pattern of inheritance (Figure 3.27). Because humans do not have as many offspring as other organisms, we may not recognize Mendelian patterns as easily. However, understanding these principles and being able to calculate the probability that an offspring will have a Mendelian phenotype is still important.
Figure 3.27: Examples of human diseases with their gene names that follow a Mendelian pattern of inheritance.
Mendelian disorder
Gene
Alpha Thalassemia
HBA1
Cystic Fibrosis
CFTR
Fragile X Syndrome
FMR1
Glucose-6-Phosphate Dehydrogenase Deficiency
G6PD
Hemophilia A
F8
Huntington disease
HTT
Mitochondrial DNA Depletion Syndrome
TYMP
Oculocutaneous Albinism: Type 1
TYR
Polycystic Kidney Disease
PKHD1
Sickle-cell anemia
HBB
Spinal Muscular Atrophy: SMN1 Linked
SMN1
Tay-Sachs Disease
HEXA
Wilson Disease
ATP7B
Example of Mendelian Inheritance: The ABO Blood Group System
In 1901, Karl Landsteiner at the University of Vienna published his discovery of ABO blood groups. While conducting blood immunology experiments in which he combined the blood of individuals who possess different blood cell types, he observed an agglutination (clotting) reaction. The presence of agglutination implies there is an incompatible immunological reaction; no agglutination will occur in individuals with the same blood type. This work was clearly important because it resulted in a higher survival rate of patients who received blood transfusions. Blood transfusions from someone with a different type of blood causes agglutinations, and the resulting coagulated blood can not easily pass through blood vessels, resulting in death. Landsteiner received the Nobel Prize (1930) for his discovery and explaination of the ABO blood group system.
Blood cell surface antigens are proteins that coat the surface of red blood cells, and antibodies are specifically “against” or “anti” to the antigens from other blood types. Thus, antibodies are responsible for causing agglutination between incompatible blood types. Understanding the interaction of antigens and antibodies helps to determine ABO compatibility amongst blood donors and recipients. To better comprehend blood phenotypes and ABO compatibility, blood cell antigens and plasma antibodies are presented in Figure 3.28. Individuals that are blood type A have A antigens on the red blood cell surface, and anti-B antibodies, which will bind to B antigens should they come in contact. Alternatively, individuals with blood type B have B antigens and anti-A antibodies. Individuals with blood type AB have both A and B antigens but do not produce antibodies for the ABO system. This does not mean type AB does not have any antibodies present, just that specifically anti-A and anti-B antibodies are not produced. Individuals who are blood type O have nonspecific antigens and produce both anti-A and anti-B antibodies.
Figure 3.29 shows a table of the ABO allele system, which has a Mendelian pattern of inheritance. Both the A and B alleles function as dominant alleles, so the A allele always codes for the A antigen, and the B allele codes for the B antigen. The O allele differs from A and B, because it codes for a nonfunctional antigen protein, which means there is no antigen present on the cell surface of O blood cells. To have blood type O, two copies of the O allele must be inherited, one from each parent, thus the O allele is considered recessive. Therefore, someone who is a heterozygous AO genotype is phenotypically blood type A, and a genotype of BO is blood type B. The ABO blood system also provides an example of codominance, which is when both alleles are observed in the phenotype. This is true for blood type AB: when an individual inherits both the A and B alleles, then both A and B antigens will be present on the cell surface.
Also found on the surface of red blood cells is the rhesus group antigen, known as “Rh factor.” In reality, there are several antigens on red blood cells independent from the ABO blood system, however, the Rh factor is the second most important antigen to consider when determining blood donor and recipient compatibility. Rh antigens must also be considered when a pregnant mother and her baby have incompatible Rh factors. In such cases, a doctor can administer necessary treatment steps to prevent pregnancy complications and hemolytic disease, which is when the mother’s antibodies break down the newborn’s red blood cells.
An individual can possess the Rh antigen (be Rh positive) or lack the Rh antigen (be Rh negative). The Rh factor is controlled by a single gene and is inherited independently of the ABO alleles. Therefore, all blood types can either be positive (O+, A+, B+, AB+) or negative (O-, A-, B-, AB-).
Individuals with O+ red blood cells can donate blood to A+, B+, AB+, and O+ blood type recipients. Because O- individuals do not have AB or Rh antigens, they are compatible with all blood cell types and are referred to as “universal donors.” Individuals that are AB+ are considered to be “universal recipients” because they do not possess antibodies against other blood types.
Mendelian Patterns of Inheritance and Pedigrees
A pedigree can be used to investigate a family’s medical history by determining if a health issue is inheritable and will possibly require medical intervention. A pedigree can also help determine if it is a Mendelian recessive or dominant genetic condition. Figure 3.30 is a pedigree example of a family with Huntington’s disease, which has a Mendelian dominant pattern of inheritance. In a standard pedigree, males are represented by a square and females are represented by a circle. Biological family members are connected to a horizontal line, with biological parents above and offspring below. When an individual is affected with a certain condition, the square or circle is filled in as a solid color. With a dominant condition, at least one of the parents will have the disease and an offspring will have a 50% chance of inheriting the affected chromosome. Therefore, dominant genetic conditions tend to be present in every generation. In the case of Huntington’s, some individuals may not be diagnosed until later in adulthood, so parents may unknowingly pass this dominantly inherited disease to their children.
Because the probability of inheriting a disease-causing recessive allele is more rare, recessive medical conditions can skip generations. Figure 3.31 is an example of a family that carries a recessive cystic fibrosis mutation. A parent that is heterozygous for the cystic fibrosis allele has a 50% chance of passing down their affected chromosome to the next generation. If a child has a recessive disease, then it means both of their parents are carriers (heterozygous) for that condition. In most cases, carriers for recessive conditions show no serious medical symptoms. Individuals whose family have a known medical history for certain conditions sometimes seek family planning services (see the Genetic Testing section).
Pedigrees can also help distinguish if a health issue has either an autosomal or X-linked pattern of inheritance. As previously discussed, there are 23 pairs of chromosomes and 22 of these pairs are known as autosomes. The provided pedigree examples (Figure 3.30–31) are autosomally linked genetic diseases. This means the genes that cause the disease are on one of the chromosomes numbered 1 to 22. The conditions caused by genes located on the X chromosome are referred to as X-linked diseases.
Figure 3.32 depicts a family in which the mother is a carrier for the X-linked recessive disease Duchenne Muscular Dystrophy (DMD). The mother is a carrier for DMD, so daughters and sons will have a 50% chance of inheriting the pathogenicDMD allele. Because females have two X chromosomes, females who inherit only one copy will not have the disease (although in rare cases, female carriers may show some symptoms of the disease). On the other hand, males who inherit a copy of an X-linked pathogenic DMD allele will typically be affected with the condition. Thus, males are more susceptible to X-linked conditions because they only have one X chromosome. Therefore, when evaluating a pedigree, if a higher proportion of males are affected with the disease, this could suggest the disease is X-linked recessive.
Compared to the X chromosome, the Y chromosome is smaller with only a few genes. Y-linked traits are therefore rare and can only be passed from a chromosomal father to a biological XY child.
