Gregor Mendel's research with genes and the way they work together allowed future
research in the field of genetics to develop. He began his research
when he entered a monastery which was administered by an Abbot.
The Abbot did work in plant breeding, and Mendel's interest in
this subject began when the Abbot held a course in crossbreeding plants. After Mendel participated in this course, he left the
monastery to study math and physics at the University of Vienna.
Two years later Mendel left Vienna to return to the monastary where he began his own experiments with pea plants. In 1865, he wrote a paper entitled "Experiments with Plant Hybrids" which was published in the journal of a local natural history society. This paper showed that each organism has physical traits that correspond to invisible elements within the cell. These invisible elements, which we now called genes, exist in pairs. Mendel showed that only one member of this genetic pair will be passed on to each individual offspring. The gene is incorporated into a sperm or egg cell. All of Mendel's reasoning and findings were deduced with no knowledge of anything that we know today such as chromosomes, cell structure, fertilization, mitosis, or meiosis. Many people say that Mendel's findings were quite avant-garde because they could not be placed in any sort of biological framework; they were the first observations of such a kind.
In his research, Mendel studied phenotypes instead of genotypes because he did not yet know what genes were. In fact, the concept of a gene did not even exist. Phenotypes are the traits that are outwardly expressed and measurable. A genotype, on the other hand, is the direct blueprint of genetic material. Some examples of phenotypic traits are hair color and eye color, the number of fingers we have, and behavioral traits such as the way we walk, smile, etc. They also can be physiological traits such as heart rate or biochemical traits such as cholesterol level.
Mendel chose peas for his studies because they were easy to culture and they had many offspring per mating. They also are capable of self-fertilization and there are different varieties of peas available to study through cross-breeding. Mendel was extremely careful in gathering his data and scrutinizing the results of every experiment. This attention to detail along with his mathematical insight allowed Mendel to reach his conclusions.
When doing his work, Mendel posed questions on how physical characteristics of peas were transmitted from generation to generation and whether these transmissions were unchanged or altered when passed on. He also questioned whether hereditary particles existed. Mendel pondered all of these questions while doing his experiments.
His studies were based on seven traits of peas. The seven traits were qualitative (they could be measured and a value assigned), therefore, specified qualities could be assigned to each plant. These characteristics were visible and it was through them that he could study the effects of reproduction.
The seven traits were:
Mendel began his experiments using a set of pure-breeding pea plants. This meant that for every plant that he self-fertilized, he made sure that the resulting plant had the exact phenotype of its parents. He performed monohybrid crosses which meant that the experiment was carried out between two strains of plants that differed only in one characteristic. He crossed parents of different phenotypes to see what resulted. The parents were denoted by a P, while the offspring were called the filial generation. F1 is the first filial generation and similarly, offspring of the F1 generation are the F2 generation and so on.
When Mendel conducted his experiments to generate the F1 generation using monohybrid crosses, all of the F1s resembled one of the parental types every time. For instance, when testing for the shape of the seed, he combined one P round seed with one P wrinkled seed - all of the F1 offspring were round. When he found that one trait, in this case, wrinkled, was not represented in the offspring, he called this a recessive trait. This meant that the round trait was dominant over the wrinkled trait. This idea is now referred to as Mendel's Law of Dominance. When doing these experiments, Mendel also observed that the sex of the parent bore no importance to the trait exhibited in the offspring. A cross between a male round pea plant with a female wrinkled pea plant would give identical results to a female round crossed to a male wrinkled. This is known as Mendel's Law of Parental Equivalence.
Mendel found new principles in that the phenotypes absent in the F1 generation reappeared in approximately 1/4 of the F2 offspring. Mendel could not predict what traits would be present in any one individual, but he did deduce that there was a 3:1 ratio in the F2 generation for dominant/recessive phenotypes.
When Mendel described his results, he used the term elementen which he postulated to be hereditary particles which are transmitted unchanged between generations. Although these may control certain traits, every particle or factor is not always expressed generation after generation. We now call these "factors" alleles, and an allele that can be suppressed is called a recessive allele, while one that is expressed without fail is known as a dominant allele.
Homozygous individuals are those who contain two identical alleles while heterozygous individuals are those who contain different alleles.
Mendel observed that although the dominant trait was the one expressed in the F1 generation, the recessive trait still retained its importance and would be able to be passed on fully to an F2 generation. Mendel developed a kind of shorthand for distinguishing alleles. They are designated by one or more letters. The first letter of abbreviation of a dominant allele is uppercase, for instance Rfor round seeds, and the first letter of abbreviation for a recessive allele is lowercase, i.e. r for wrinkled seeds. Thus, two alleles can result in three different genotypes: RR, Rr, and rr. RR and Rr have the same outward appearance, however, because the dominant trait is the one expressed.
Sometimes mating results can be expressed in the form of a Punnett Square
R |
r |
|
|---|---|---|
R |
RR |
Rr |
r |
rR |
rr |
Each of the boxes shows that there is a 25% chance that each result will occur. Because 3 of the 4 boxes have an R (dominant) phenotype, it explains Mendel's results. The ratio of dominant to recessive phenotypes is 3:1.
Mendel's Law of Segregation states that every pair of alleles maintains its own integrity, regardless of whether each of them are expressed. At reproduction, only one allele of a pair is transmitted to each gamete, and which allele is passed on is passed entirely by chance.
After his monohybrid crosses, Mendel did a series of dihybrid crosses. These were crosses between strains identical except for two
characteristics. For example, Mendel did experiments with round/wrinkle
(R/r) and yellow/green (Y/y). Mendel crossed a double dominant P(RRYY) with a double recessive P(rryy). All of the F1s that resulted from this were thus RrYy
and had the characteristics of round and yellow. These double
heterozygotes were then used to make an F2 generation.
Mendel observed that each of the traits he was following sorted themseleves independently. Mendel's Law of Independent Assortment states that characteristics which are controlled by different genes will assort independent of all others. Whether or not a seed will be Rr or RR has nothing to do with whether or not it will be Yy or yy.
Although Mendel did not do experiments with humans, we know now that humans have approximately 100,000 genes. The reason that we are all so different and can even look very different from both of our biological parents is because there are so many different genetic combinations that can result. It is possible to generate about 8 million different types of gametes from a person who is heterozygous for only one gene on each pair of 23 chromosomes!
These laws Mendel discovered held true most of the time. However, there are instances where they are defied. Sometimes, within a population, more than two alleles will occur at a particular locus. This is multiple allelism and occurs in such instances as the ABO blood group which has at least three common alleles and some that are more rare.
In some heterozygous organisms, both alleles are expressed, and this is termed codominance. When one characteristic is reduced in a heterozygous organism, the alleles exhibit partial or incomplete dominance because there is more than one trait being expressed. We see partial dominance in nature is some flower colors. When we see pink flowers, the allele for red is present only one time instead of two, resulting in the presence of only half the amount of red pigment.
Not all inheritance is not dependent solely on the copy of a single gene. Some characteristics, such as height, depend on the way in which many of the genes interact in an organism.
The Law of Independent Assortment described above does not apply to all situations. On a given chromosome, there are sets of genes, and genes that are on the same chromosome are physically linked to one another. During reproduction, these linked genes tend to be transmitted as a unit instead of independently. Although these links may break during meiosis, this is not always the case, and thus, the Law of Independent Assortment does not always hold true. Independent assortment sometimes occurs when genes are located on the chromosome but are relatively far apart from one another.
Mutations sometimes occur in a gene. A mutation simply is a change in the sequence of a gene. It can be due to a change in a base (letter) of the gene or due to an insertion or deletion of a piece of DNA. Although mutations occur in reproduction, the probability of one gene changing in one cell cycle is less than one in a million. Because these occurrences are so rare, Mendel did not have any problems with his results.
Mendel's paper provided much valuable information for future scientists. It was the only information on the subject Mendel wrote, however, because when the Abbott died in 1868, Mendel stopped all of his scientific work and took over the monastery.
Because humans reproduce so infrequently and have such a long lifetime, it is more difficult to study genetic disorders in humans. Instead of experimental biology, genetics is studied in humans through pedigree analysis.
In a pedigree diagram, the circle represents a female, while each square represents a male. Diamonds represent an indeterminate or unknown sex. Every row represents a single generation, and these are labeled with Roman numerals. Couples within the generation are listed from left to right across the line, and horizontal lines connect the reproductive partners. Vertical lines that descend from these pairs are indicative of offspring from the two parents. Individuals demonstrating a specific phenotype are indicated with filled shapes.
Mating between blood relatives often causes genetic disorders. This is because descendants of an individual who is a carrier for a specific disease have a much greater chance of inheriting the disease than the normal person. When close relatives mate, it therefore increases the chances of disease and mutation. Most humans, researchers say, carry within them four or five deleterious alleles in the heterozygous condition. Because relatives often carry the same deleterious alleles in this condition, there is greater likelihood that these alleles will pair up and be passed along to offspring. Thus, the taboo subject of inbreeding does have validity.
Autosomal recessive traits are those that are expressed regardless of sex - both males and females are equally likely to be afflicted. Albinism is an autosomal recessive human disease. This occurs about once in 30,000 births, and the babies are born with extremely white skin and hair color. All groups of vertebrates, and plants and insects have instances of albinism. In some species, the eyes are red because of the presence of hemoglobin (rabbits). These organisms lack the presence of the pigment melanin which gives our skin its tone. Albino individuals must be extremely careful about skin cancer and sunburn because of the absence of this protective pigment in their skin.
Phenylketonuria (PKU) is another disease that occurs approximately 1 in 5-6,000 births. Phenylalanine is a required amino acid, and phenylalanine hydroxylase metabolizes phenylalanine. Because individuals with PKU lack this enzyme, there is an accumulation of phenylalanine in blood and a related substance in urine, and this is the condition of PKU. Forty states now require that infants be tested for this trait, as it is detected easily through a simple blood test measuring phenylalanine levels. The reason it is required is because after the first few weeks of birth, if it is not treated, the high phenylalanine levels can cause mental retardation. If found early enough, it can be treated through a special diet that monitors the intake of phenylalanine. There have been ethical questions presented about whether or not testing should be completely monitored because of the cost. The regulation of mothers with PKU who carry fetuses that might be damaged by the high phenylalanin in the mother's blood raises a difficult ethical question.
Cystic Fibrosis is another disease detectable in infants at birth. It is the most common genetic disorder in Caucasians in the U.S where it afflicts approximately 1 in 2000 people. This is considered a very high frequency because most CF patients never reproduce and the disease occurs for unknown reasons. There is much research being conducted on this disease right now. In 1989, the gene for CF was isolated and sequenced. It has been found to be a large membrane protein that regulates water and salt balance in the cells. It prevents chloride ions from exiting the cells and this results in excess water inside the cells. This leads to a thick dry mucous in the lungs and other secretory tissues which causes the lungs and intestines of these patients to become clogged. Bacteria can grow in these thick secretions and can cause fatal lung problems.
There is a test available to determine if a potential parent is heterozygous for the CF allele, but this test is only 75% accurate. Thus, it causes problems for the parents and poses questions such as "Should you take this test?" and "What will you do if the results are positive?" Researchers are continuing to research this disease to try to find a cure for CF patients.
Sickle-cell Trait
Sickle-cell anemia is another disease that afflicts mainly African-Americans. This occurs as a result of a mutation in a hemoglobin gene. Hemoglobin is a protein that has four subunits - two alpha and two beta. Hemoglobin carries oxygen throughout the body inside red blood cells (RBCs). The mutation causes the hemoglobin to crystallize inside the RBC, which leads to fragile sickle-shaped red blood cells that become entangled with one another and can lead to clotted blood vessels. This can lead to oxygen deficiency which results in mental retardation or heart failure because the heart has to work harder to pump the thicker blood. Because of oxygen deficiency, there are often problems in joints as well.
Although malaria is a disease that has been eliminated in the U.S, it still causes many deaths in Africa. Malaria occurs as a result of a parasitic protozoan which lives in red blood cells. Malaria does not occur in individuals with sickle cell anemia because the sickled red blood cells do not provide a place where the malaria parasite flourishes. Thus, this deleterious trait has provided some survival advantage to those who carry it as a heterozygote.
Most people have very limited knowledge of genetics in general, and do not know about those diseases which are a result of genetic complications. Furthermore, they are not educated about the counseling available to them. There are new diagnostic and therapeutic treatments emerging all the time. Genetic counselors help families to understand the genetic disorder and provide counseling on how to deal with the knowledge. They also can advise on the risks that may be presented to children or other relatives. The counselors are there solely to educate the families and not to make the decisions for them. They just help them make more educated decisions and help them to learn about all of their options.
Modern treatment of diseases and prevention of them are constantly emerging. The increased knowledge also presents complex ethical issues and problems for the families. These dilemmas occur primarily in prenatal diagnosis of diseases. This presents questions of abortion and whether or not a parent should have a right to terminate a pregnancy of a child who may be terminally ill.
There are also traits that are a result of autosomal dominant inheritance. These are those such as Neurofibromatosis or NF. This afflicts 1 in 3,500 people. The disease is characterized by hundreds of non-malignant tumors all over the body and by abnormal bone growth. This disease, unlike some others, cannot be diagnosed prenatally and cannot be cured. Patients can become blind and deaf if these tumors grow on the spinal cord. The gene was discovered in 1990, and they are working on a test and a cure.
The quality of earwax is also an autosomal dominant trait. It is an innocuous phenotype that has two forms. There is wet, sticky earwax and dry earwax. Wet earwax is a result of a single dominant gene (WW or Ww). Dry earwax is from the result of ww combination. Wet earwax is associated with armpit odor and is more common in Caucasians and Blacks (80-90% wet earwax). Dry earwax is more common in Asians (94% dry earwax). Mammals, including humans, tend to choose their mates based in part on scent, and it is postulated that Asians have choosen their mates (in part) based on body aroma. The gene for earwax infulences secretions from apocrine glands, which include the mammary glands. Research shows that there is double the rate of occurrence for breast cancer in Japanese women with wet earwax as opposed to dry earwax, suggesting that the gene may somehow be involved in breast cancer. This hypothesis is supported elsewhere, because the occurence of breast cancer in a population is directly related to the predominance of wet earwax.
Blood groups vary among individuals as well, and this is due to genetics. Blood groups are a result of molecules on the surface of the blood cells. These molecules are known as antigens, and they are attacked by antibodies when in a different individual. The ABO blood group is the most common, and it consists of three alleles. A and B are both codominant, and O is the absence of both A and B. Individuals do not have antibodies to their own RBC surface antigens. It is because of these blood groups that there emerged an initial understanding of why some blood transfusions worked and others were fatal. People have different blood types, and individuals can accept only certain types of blood - type OO being the universal donor, and type AB being the universal acceptor. Blood type is also used in criminal investigation.