Physiological Determinants of Global Health

CONTENTS OF CURRICULUM UNIT 15.06.04

  1. Unit Guide
  1. Rationale
  2. Content Objectives
  3. Classroom Strategies
  4. Classroom Activities
  5. Notes
  6. Bibliography
  7. Appendix

Genetics and Mechanisms of Disease

Corryn Nikodemski

Published September 2015

Tools for this Unit:

Content Objectives

Cells

This unit is designed for sixth grade students. In my district, students are not exposed to cell theory until seventh grade. However, since I am responsible for teaching about organs and their systems, occasionally it is appropriate for me to discuss something that happens at a cellular level. This is a significant motivating factor since I plan to use this as an enrichment unit during Response to Intervention time and will most likely have students whom are at or above grade level. Therefore, the content begins with background on cells as the basic unit of life.

According to cell theory, all living things are made up of cells (they are the basic unit of life), and all cells are produced from other cells. The production of new cells occurs in a process called cell division and it results in genetic material being passed from parent cell to daughter cell. Cell division occurs my mitosis or meiosis. Mitosis occurs in somatic (body) cells, whereas meiosis occurs in germ-line (reproductive) cells. While my students will not be assessed on their understanding of cell division, it would be helpful for them to know that two types of division take place, and that one type, meiosis, is essential for human reproduction. The cells that result from meiosis are special types of cells called gametes, or what are commonly known as egg and sperm cells.

Multicellular organisms, such as humans, contain different kinds of cells that are specialized at doing jobs to sustain life. For instance, cardiac muscle cells drive the contractions that allow the heart to beat. Red blood cells carry a protein called hemoglobin and are specially shaped like flattened disks. This allows them to efficiently transport oxygen molecules. Special rod and cone cells in your eyes allow you to see colors and give us night vision. Nerve cells connect to muscle cells to allow you to move your fingers to access this unit using your keyboard or mouse.

The cells that make up the human body are classified as eukaryotic cells. Eukaryotes can then be subdivided into plant and animal cells. Distinguishing characteristics between the two include a fixed shape cell wall and the presences of chloroplasts in plant cells. Animal cells are not fixed in shape, but still contain a cell membrane and specialized organelles such as the nucleus, mitochondria, endoplasmic reticulum, Golgi bodies and ribosomes (see Figure 1). Each of these organelles conducts important functions in cell processes, and therefore plays a role in health. The cytoplasm inside the cell contains both the cytosol (fluid-filled space) and the organelles. 1

Figure 1

The nucleus of a cell contains all the genetic material to direct functions of the cell. It is often compared to the brain; its primary function being to give directions for physiological processes that will keep itself alive. In addition to the nucleus, cells also contain ribosomes, which aid in protein synthesis and function within the cytoplasm of the cell. This protein synthesis occurs when DNA is transcribed to mRNA and proteins are created by the translation of mRNA. The ribosomes are attached to the rough endoplasmic reticulum (ER) and are the sites of protein synthesis. ER is mainly acts as a storage facility, but also help with the creation of lipids and steroids.2 Vesicles are pieces of smooth ER are capable of transporting their contents around the cells. Mitochondria are responsible for cellular respiration and providing energy for the cell to continue life, while Golgi bodies modify, process, and sort newly produced proteins that arrive from the ER.3

DNA and the Nucleus

The genomic DNA, or set of DNA instructions within a cell, is contained with the nucleus. DNA is made up of a series of nucleotides. DNA in the nucleus is arranged as a double helix (Figure 2). Nucleotides contain a sugar, a phosphate, and a nitrogenous base. These are put together like a puzzle to form DNA molecules. During the life of a cell, the instructions encoded in genes on DNA are first transcribed into mRNA, and then translated into proteins. Thus, the instructions embedded in DNA within the cell nucleus are used throughout the life of a cell to generate new proteins.

Human DNA is a long molecule in which the instructions for making proteins are written in a language consisting of four acid bases (adenine, guanine, cytosine, and thymine). The linear sequence written by the four chemical characters make up what is referred to as your genotype. The order of the paired bases specifies the codes for genes, which are translated into proteins, which dictate your phenotype, or how you look and behave. The combination of these organic bases reads like a code, but even with all the genetic variations around us, over 99% of our DNA is exactly the same among individuals. This means our genotypes are 99% similar. The human genome contains over three billion base pairs, so less that one percent of them are different in each human. However, that one percent is enough to account for all of the phenotypic diversity in the human population. 4

These base pairs are arranged on the DNA molecule into a specific structure called the double helix. At the molecular level, these bases pair with each other (A and T, C and G), and are bonded with sugar and phosphate molecules. These base pairs are bundled, called genes, and packaged into groups called chromosomes. On each chromosome, there is a “discrete” location for each gene. Chromosomes are what determine whether someone is a male or a female. As stated in Biology: Exploring Life:

The existence of chromosomes as pairs of homologs explains why each body cell has two copies of each allele. The separation of homologous chromosomes during meiosis accounts for the presence of only one pair of alleles in a gamete.5

When genes are passed from parent to offspring, all the genetic information from each of the two parent cells is “inherited” to the daughter cell. In the nucleus of a fertilized human egg cell, there are twenty-three pairs of structures called chromosomes. When fertilization occurs, each gamete, carrying half of this information (half in the egg and half in the sperm), come together to form the new cell. The mixing of the genetic information, during meiosis, from each parent cell is what allows for variation to keep the population sustained. This variation allows for some individual to have a survival advantage over others in the same population, thus driving evolution. These patterns of inheritance are described by scientists in graphical models such as the pedigree and Punnett square.

Special chromosomes called sex chromosomes determine gender in most animals. Females generally have two X chromosomes and males have an X and a Y chromosome (XY). Therefore, some diseases that are considered linked to the X chromosome are expressed when a male receives a recessive X allele on his X chromosome.

Figure 2: An Inside Look of a Cell

Chromosomes, Heredity, and Mendelian Genetics

Chromosomes are the “suitcases” of DNA. They contain DNA and “unpack” it during cellular reproduction. A disease is considered “inherited” when it occurs because of the pattern of inheritance during reproductive processes. When an egg is fertilized, it receives an allele for each gene from each parent, and depending on the combination received, the new human is afflicted with the disease, a carrier for the disease, or may receive no genetic information related to the disease. In a given family situation for a recessive autosomal disease like HSAN, if both parents are heterozygous for a disease (meaning they carry a dominant and a recessive allele), a child will be born with the disease if the gametes that fertilize both happen to have the recessive allele. A child can be a carrier of the disease, but not affected, if he or she receives one dominant and one normal allele. 6

People have known diseases can be “passed” from parents to offspring for a long time, but they weren’t sure how. In early Judaism, if two sisters lose a son as the result of the excessive bleeding after circumcision, they are not required to have subsequent sons circumcised. This exemption to a religious regulation demonstrates an earlier acknowledgement of hemophilia as an inheritable disease.7

While all diseases that present at birth are called congenital diseases, not all are considered inherited. For instance, if a baby is born with a ventricular septum defect (commonly called a “hole in the heart), it could be due something that occurred during somatic cell division during gestation. Other examples of congenital defects include spina bifida, club foot, and gastroschisis (when intestines present outside the abdomen). Adults that displayed these conditions as children can produce offspring with no chance of having the defect since it was not inherited.

The graphical models of the patterns displayed through the passing of genes are most commonly known as Punnett squares. Created in 1900 by Gregor Mendel, Punnett squares are some of the most familiar organizers used to discuss inheritance trends. Using controlled experiments, Mendel provided evidence that certain phenotypes could be created through careful mating of parent organisms.

Mendel’s conclusions were drawn from experiments he conducted with pea plants. He chose to examine seven traits including height, seed color, flower color, and others. In order to begin, he had to be sure the plants were self-fertilized and would not produce plants that had characteristics different than the parent plant.8 To start, he completed mono-hybrid crosses of plants that would only cross one type of characteristic (example: seed color). The data analysis of these monohybrid crosses led to the generation of new vocabulary such as dominant/recessive trait, P generation, and F1 generation. Dominant trait refers to the characteristic that was displayed, while recessive trait refers to the characteristic that seemingly disappeared when plants with two different characteristics were mated (example: yellow is dominant to green for seed color.) A “P generation” is the original parental generation, and the “F1 generation” is the first round of offspring (F1= first filial).

When he crossed the plants for a second time (the F2 generation), he found that the recessive traits that had disappeared showed up again in a special ratio of 3:1. This ratio was found in each of the seven traits he studied. This reappearance conflicted with the theories on inheritance that were current at that time, which stated that genetic characteristics were a true “blending” of fluids. Mendel eventually hypothesized that the traits in plants were governed by factors that were derived from each parent. The term allele is now used to describe this factor. Additionally, while the traits may not show up in the individual, they can show up in later generations.9

In a monohybrid cross, during which on a single trait is crossed, hereditary patterns follow specific patterns as shown in Figure 3. This shows a homozygous recessive trait (small y, green) being crossed with a heterozygous dominant trait (capital Y, yellow).

Figure 3: A Monohyrbid Cross Punnett Square

In a dihybrid cross, organisms with two specific traits are crossed. These produce more complex Punnett squares as shown in Figure 4. A dihybrid cross also illustrates the law of Independent Assortment as discussed below.

RA

Ra

rA

Ra

RA

RRAA

RRAa

RrAA

RrAa

Ra

RRAa

RRaa

RrAa

Rraa

rA

RrAA

RrAa

rrAA

rrAa

Ra

RrAa

Rraa

rrAa

Rraa

Figure 4: A Dihybrid Cross Punnett Square

Both of these squares illustrate two of Mendel’s Laws. The first Law of Segregation refers to the fact that pairs of chromosomes separate from the two members, and one member determines the genetic make-up of each gamete. 10 When there are two alleles for a trait, the fertilized cell will be either homologous or heterozygous for that specific trait. If an allele is dominant, that means that it will be expressed over an allele that is recessive: therefore, in heterozygous cells, the dominant trait will be expressed. Mendel’s second Law of Independent Assortment states that the pairs of chromosomes that are inherited are done so independent of one another, so that different traits have an equal opportunity of occurring together.11

Mutation

The complications that arise with genetic inheritance in humans create many more questions that new frontiers of biomedical research are trying to answer. Some of these complications are called mutations. These occur when extra copies of genes are present, when copies of genes are missing, or when the sequence within a gene gets altered in some way. In fact, mutations account for all biological evolution. New alleles form either randomly or in response to the environment. New mutations lead to offspring that are born with a new trait and thus the gene pool is diversified.

While some new traits can be devastating, as is the case with HSAN, other mutant traits can also allow for adaptations and survival. One of the best-known examples of a mutant trait offering a favorable outcome occurs in the peppered moth. During the Industrial Revolution, as the air became polluted with dark soot, a dark form of peppered moth began to flourish. Scientists believe this resulted because predatory birds could not see it against the soot-covered surfaces. Using a linkage map, scientists are hoping to find the exact mechanism for the mutation.12

Other mutations create outcomes that are not favorable. In humans. single gene defects can cause diseases such as sickle-cell anemia and phenylketonuria (PKU), both of which can be fatal. If detected early, during a newborn screening test, infants with PKU can be given a special diet. The gene mutation linked to PKU is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine. When a person with this defect eats a diet high in protein, a dangerous build up of amino acids can put them at a high risk of issues like intellectual disabilities, neurological problems, and poor bone strength among others.13

Disease

After I teach my students the basics of DNA, chromosomes, and genetics, I will have them apply the information by reading medical texts on genetic diseases (cystic fibrosis and HSAN) and their impact on various body systems.

Cystic Fibrosis occurs when a person inherits a defective gene on chromosome seven called CFTR (cystic fibrosis transmembrane conductance regulator). The disease is recessive, which means both parents must have the defective gene for their children to get the disease. It primarily affects Caucasians, for reasons still unknown, but occurs because both the father and the mother have a recessive allele on one copy of chromosome seven. If only one has the gene, the child may become a carrier. One of many mutations that cause cystic fibrosis is a three base deletion. This means that a certain amino acid is not present within the protein produced in cells.14

The gene that is affected in CF is responsible for chloride transport in and out of cells. When chloride transport is impaired, mucus builds up outside the cells in the airway of the lung, and other places. While I originally believed cystic fibrosis only affected the lungs, it can also cause mucus build up in the digestive tract. This build up can affect enzymes ability to break down food, which in turns causes issues with nutrition absorption. Therefore, people affected with cystic fibrosis not only have a compromised respiratory system, but also have digestive system that does not function properly.15  

The other genetic disease that I found interesting is the one that was mentioned at the start of this unit. HSAN is a class of diseases that affect the sensory and autonomic nervous systems. There are multiple classes of the disease, but the class that we discuss is autosomal recessive. The protein that helps nerve cells create myelin produces in an abnormal manner. This causes defects in the development of the nerve cells that detect pain and temperature. This is generally diagnosed in infants when self-destructive behaviors occur and the baby does not respond in a typical manner. For instance, the baby may bite his or her tongue or fingers, but does not cry.16

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