Mendelian Genetics Reading

Gregor Mendel published his notes in 1865 and 1866. His work underlies the modern genetics we have today.

Mendel was an Augustinian priest and scientist, and is often called the father of genetics for his study of the inheritance of traits in pea plants. Mendel showed that the inheritance of traits follows particular laws, which were later named after him. The significance of Mendel's work was not recognized until the turn of the 20th century. Its rediscovery prompted the foundation of the discipline of genetics. He is known as the "father of modern genetics", was inspired by both his professors at university and his colleagues at the monastery to study variation in plants, and he conducted his study in the monastery's garden. Between 1856 and 1863 Mendel cultivated and tested some 29,000 pea plants (i.e. Pisum sativum). This study showed that one in four pea plants had purebred recessive alleles (Homozygous recessive) two out of four were hybrid (heterozygous) and one out of four were purebred dominant (homozygous dominant). His experiments brought forth two generalizations which later became known as Mendel's Laws of Inheritance.

The Law of Segregation, also known as Mendel's First Law, essentially has three parts.

Alternative versions of genes account for variations in inherited characteristics. This is the concept of alleles. Alleles are different versions of genes that impart the same characteristic. For example, each human has a gene that controls eye color, but there are variations among these genes in accordance with the specific color for which the gene "codes".
For each characteristic, an organism inherits two alleles, one from each parent. This means that when somatic cells are produced from two alleles, one allele comes from the mother and one from the father. These alleles may be the same (true-breeding organisms/homozygous e.g. ww and rr in Fig. 3), or different (hybrids/heterozygous, e.g. wr in Fig. 3).
The two alleles for each characteristic segregate during gamete production. This means that each gamete will contain only one allele for each gene. This allows the maternal and paternal alleles to be combined in the offspring, ensuring variation.

Law of Independent Assortment, also known as Mendel’s Second Law

The Law of Independent Assortment, also known as "Inheritance Law" or Mendel's Second Law, states that the inheritance pattern of one trait will not affect the inheritance pattern of another. While his experiments with mixing one trait always resulted in a 3:1 ratio (Fig. 1) between dominant and recessive phenotypes, his experiments with mixing two traits (dihybrid cross) showed 9:3:3:1 ratios (Fig. 2). But the 9:3:3:1 table shows that each of the two genes are independently inherited with a 3:1 ratio. Mendel concluded that different traits are inherited independently of each other, so that there is no relation, for example, between a cat's color and tail length. This is actually only true for genes that are not linked to each other.

Independent assortment occurs during meiosis I in eukaryotic organisms, specifically anaphase I of meiosis,^[3] to produce a gamete with a mixture of the organism's maternal and paternal chromosomes. Along with chromosomal crossover, this process aids in increasing genetic diversity by producing novel genetic combinations.

Of the 46 chromosomes in a normal diploid human cell, half are maternally-derived (from the mother's egg) and half are paternally-derived (from the father's sperm). This occurs as sexual reproduction involves the fusion of two haploid gametes (the egg and sperm) to produce a new organism having the full complement of chromosomes. During gametogenesis - the production of new gametes by an adult - the normal complement of 46 chromosomes needs to be halved to 23 to ensure that the resulting haploid gamete can join with another gamete to produce a diploid organism. An error in the number of chromosomes, such as those caused by a diploid gamete joining with a haploid gamete, is termed aneuploidy.

In independent assortment the chromosomes that end up in a newly-formed gamete are randomly sorted from all possible combinations of maternal and paternal chromosomes. Because gametes end up with a random mix instead of a pre-defined "set" from either parent, gametes are therefore considered assorted independently. As such, the gamete can end up with any combination of paternal or maternal chromosomes. Any of the possible combinations of gametes formed from maternal and paternal chromosomes will occur with equal frequency. For human gametes, with 23 pairs of chromosomes, the number of possibilities is 2^23 or 8,388,608 possible combinations.The gametes will normally end up with 23 chromosomes, but the origin of any particular one will be randomly selected from paternal or maternal chromosomes. This contributes to the genetic variability of progeny.

Figure 1: Dominant and recessive phenotypes.
(1) Parental generation. (2) F₁ generation. (3) F₂ generation. Dominant (red) and recessive (white) phenotype look alike in the F₁ (first) generation and show a 3:1 ratio in the F₂ (second) generation

Figure 2: The genotypes of two independent traits show a 9:3:3:1 ratio in the F₂ generation. In this example, coat color is indicated by B (brown, dominant) or b (white) while tail length is indicated by S (short, dominant) or s (long). When parents are homozygous for each trait ('SSbb and ssBB), their children in the F₁ generation are heterozygous at both loci and only show the dominant phenotypes. If the children mate with each other, in the F₂ generation all combination of coat color and tail length occur: 9 are brown/short (purple boxes), 3 are white/short (pink boxes), 3 are brown/long (blue boxes) and 1 is white/long (green box).

Figure 3: The color alleles of Mirabilis jalapa (a type of flower) are not dominant or recessive.
(1) Parental generation. (2) F₁ generation. (3) F₂ generation. The "red" and "white" allele together make a "pink" phenotype, resulting in a 1:2:1 ratio of red:pink:white in the F₂ generation.

Exceptions to the Rules:

Some alleles are neither dominant nor recessive, and many traits are controlled by multiple alleles or multiple genes.

A Mendelian trait is one that is controlled by a single locus and shows a simple Mendelian inheritance pattern. In such cases, a mutation in a single gene can cause a disease that is inherited according to Mendel's laws. Examples include sickle-cell anemia, Tay-Sachs disease, cystic fibrosis and xeroderma pigmentosa. A disease controlled by a single gene contrasts with a multi-factorial disease, like arthritis, which is affected by several loci (and the environment) as well as those diseases inherited in a non-Mendelian fashion. The Mendelian Inheritance in Man database is a catalog of, among other things, genes in which Mendelian mutants causes disease.

Sickle Cell Anemia

Sickle-cell disease or sickle-cell anaemia (or anemia) is a blood disorder characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in their restricted movement through blood vessels, depriving downstream tissues of oxygen. The disease is chronic and lifelong: individuals are most often well, but their lives are punctuated by periodic painful attacks and a risk of various other complications. Life expectancy is shortened, with older studies reporting an average life expectancy of 42 and 48 years for males and females, respectively.

Cystic Fibrosis

A hereditary disease that affects mainly the lungs and digestive system, causing progressive disability.Thick mucus production, as well as a less competent immune system, results in frequent lung infections. Diminished secretion of pancreatic enzymes is the main cause of poor growth, fatty diarrhea and deficiency in fat-soluble vitamins. Males can be infertile due to the condition congenital bilateral absence of the vas deferens. Often, symptoms of CF appear in infancy and childhood. Meconium ileus is a typical finding in newborn babies with CF.

Individuals with cystic fibrosis can be diagnosed prior to birth by genetic testing. Newborn screening tests are increasingly common and effective. The diagnosis of CF may be confirmed if high levels of salt are found during a sweat test, although some false positives may occur.There is no cure for CF, and most individuals with cystic fibrosis die young: many in their 20s and 30s from lung failure. However, with the continuous introduction of many new treatments, the life expectancy of a person with CF is increasing. Lung transplantation is often necessary as CF worsens.

Cystic fibrosis is one of the most common life-shortening, childhood-onset inherited diseases. In the United States, 1 in 3900 children are born with CF^[1]. It is most common among Europeans and Ashkenazi Jews; one in twenty-two people of European descent are carriers of one gene for CF, making it the most common genetic disease in these populations. Ireland has the highest rate of CF carriers in the world (1 in 19).CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices, and mucus. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither gene can produce a functional CFTR protein. Therefore, CF is considered an autosomal recessive disease.

Incomplete Dominance

Incomplete Dominance (pg 215-216 in your text):

Apparent blending can occur in the phenotype when there is incomplete dominance resulting in an intermediate expression of a trait in heterozygous individuals. For instance, in primroses, snapdragons, and four-o'clocks, red or white flowers are homozygous while pink ones are heterozygous. The pink flowers result because the single "red" allele is unable to code for the production of enough red pigment to make the petals dark red.

Another example of an intermediate expression may be the pitch of human male voices. The lowest and highest pitches apparently are found in men who are homozygous for this trait (AA and aa), while the intermediate range baritones are heterozygous (Aa). The child-killer disease known as Tay-Sachs is also characterized by incomplete dominance. Heterozygous individuals are genetically programmed to produce only 40-60% of the normal amount of an enzyme that prevents the disease.

Fortunately for Mendel, the pea plant traits that he studied were controlled by genes that do not exhibit an intermediate expression in the phenotype. Otherwise, he probably would not have discovered the basic rules of genetic inheritance

Environmental Influences

The phenotype of an individual is not only the result of inheriting a particular set of parental genes. The specific environmental characteristics of the uterus in which a fertilized egg is implanted and the health of the mother can have major impacts on the phenotype of the future child. For instance, oxygen deprivation or inappropriate hormone levels can cause lifelong, devastating effects. Likewise, accidents, poor nutrition, and other environmental influences throughout life can alter an individual's phenotype.

Geneticists study identical or monozygotic twins to determine which traits are inherited and which ones were acquired following conception. Since monozygotic twins come from the same zygote, they are essentially identical in their genetic makeup. If there are any differences in their phenotypes, the environment is virtually always responsible. Such differences show up in basic capabilities such as handedness, which had been assumed to be entirely genetically determined. In rare instances, one monozygotic twin will be clearly right-handed while the other will be left-handed. This suggests that there may be both genetic and environmental influences in the development of this trait

QUESTIONS: (Write ALL of the following IN YOUR WORDS. I WILL know if you’re copying and you WILL get points OFF)

1. Please describe the three parts to Mendel’s first law.

2. Explain Mendel’s second law. Why is this important?

3. Based on the reading, how do you think genetic mutations could be HELPFUL?

4. How can mutations be harmful? Give one example.

5. What is incomplete dominance? Give an example you think may be incomplete dominance (NOT FROM THIS READING).