Genetics: Mendel, his Peas and Beyond

Genetic variations form the intricate foundation of the diverse range of appearances, behaviors, and disease susceptibilities observed among individuals. Our physical traits, from the color of our eyes and hair to the shape of our noses and earlobes, are all orchestrated by the instructions embedded within our genes. Genes act as the blueprint for our development, directing how cells grow and tissues form. Some genes exhibit dominance, manifesting their traits with just one copy, while others require two copies, one from each parent, to display their characteristics.

Beyond physical appearances, genes also play a significant role in shaping our behaviors and temperaments. They influence the brain's chemistry and structure, affecting neurotransmitter levels and brain signaling. As a result, certain genetic variations can lead to preferences for specific tastes, sleep patterns, and personality traits. However, it is important to note that the interaction between genes and the environment can modify or enhance these genetic predispositions.

When it comes to disease susceptibility, genetic mutations or changes in DNA sequences can increase the risk of various conditions. Some diseases are influenced by a single gene, while others involve the interplay of multiple genes and environmental factors. Genetic variations contribute to diseases like lactose intolerance, Age-related Macular Degeneration, and many other complex conditions.

Figure 1: Typical familial inheritance percentage (HudsonAlpha Institute for Biotechnology, n.d.).

This article delves into the fascinating world of genetics, exploring how genes shape our appearances, behaviors, and disease susceptibilities. It will also examine the groundbreaking work of Gregor Mendel and his study of pea plants, which laid the foundation for our understanding of inheritance patterns. Furthermore, it will explore polygenic inheritance, where multiple genes contribute to a single trait, leading to a continuous distribution of traits rather than distinct categories. Lastly, it will examine various inheritance patterns, from dominant and recessive traits to X-linked and mitochondrial inheritance, which all contribute to the vast diversity observed among individuals. By delving into the intricate world of genetic variations, the reader can gain a deeper understanding of what makes each individual unique and how genetics shape the complexities of human life.

How do Genetic Variations Contribute to Differences in Appearance, Behavior, and Susceptibility to Diseases?

Genetic variations underpin the vast array of differences we observe among individuals in terms of appearance, behavior, and susceptibility to diseases. Every aspect of our physical appearance, from the freckles on one's skin (Sulem et al., 2007) to the attachment style of earlobes (Shaffer et al., 2017), is orchestrated by genes. These genes convey specific instructions for how cells should develop, and tissues should form. Dominant genes tend to manifest their traits with only one copy present, while recessive genes require two copies (one from each parent) to display their characteristics.

When thinking of behaviors, it becomes a bit more intricate. Genes play a definitive role in determining our brain's chemistry and structure, which inevitably influences our behaviors and even our temperaments. For instance, our genes can impact the levels and function of neurotransmitters, the brain's signaling chemicals. This genetic foundation might explain why some individuals have a natural aversion to certain tastes, like the bitterness of compounds such as phenylthiocarbamide (Kim et al., 2003), or why some individuals are inherently morning people due to the genetic influence on their circadian rhythms (Jones et al., 2019). However, while genes may predispose individuals to specific behaviors, it is the dance between these genes and the environment that either enhances, suppresses, or modifies these genetic predispositions.

Figure 2: Genes and Heredity (Exploring Nature, n.d.).

Diseases provide another lens through which we can understand genetic variations. Genetic mutations or changes in the DNA sequences can increase the risk of various conditions. For example, lactose intolerance, a condition where individuals cannot digest lactose found in milk, is due to a decrease in the production of the enzyme lactase, and this persistence or reduction of lactase after infancy is greatly determined by genetics (Ingram et al., 2009). Some diseases, like Age-related Macular Degeneration (AMD), are influenced by multiple genes, with variations in genes like Complement Factor H (CFH) linked to many AMD cases (Haines et al., 2005). Yet, it is important to remember that many diseases emerge from both genetic susceptibility and environmental triggers. Someone might inherit a genetic predisposition for a certain condition, but it will only materialize after exposure to specific environmental factors. In sum, our genes provide a foundational blueprint that delineates a plethora of traits and predispositions. However, these genetic directives frequently interact with external factors, leading to the profound diversity and intricacy we discern in human beings (Pierce, 2012). Each mechanism of genetic variation will be explained in detail later in this paper.

Mendel and his Peas

Born in 1822 in a small farming village in Austria, Gregor Mendel was the son of peasant farmers. Despite these humble beginnings, he harbored a deep fascination with the natural world around him, particularly the diversity seen in plants and animals. At 21, Mendel joined the Augustinian Abbey of St. Thomas in Brno, which became his home and the place of his revolutionary work (Orel, 1996). Mendel began experimenting with pea plants in the monastery's garden around 1856. He chose pea plants because they were easy to grow and had distinct, observable traits that were straightforward to track across generations. He looked at seven characteristics, such as the color of the pea (yellow or green), the color of the flower (purple or white), and the height of the plant (tall or short) (Griffiths et al., 2012).

Figure 3: Representation of Mendel's research (Genetics Society, n.d.).

After crossbreeding pea plants with different characteristics and observing the offspring, Mendel came up with two fundamental laws. Mendel's First Law, the Law of Segregation, describes how we inherit individual traits. Traits (like eye color or height) can be imagined as coming in pairs of instructions, one from the mother and one from the father. Each parent, however, can only pass on one of these instructions (or alleles) to their offspring. In the case of Mendel's peas, for example, a pea plant could carry a pair of "yellow" instructions or one "yellow" and one "green". But when it comes to producing the next generation, each parent plant gives only one instruction for the color of the peas. If the offspring receives "yellow" from both parents, it will be yellow. But if it gets "yellow" from one and "green" from the other, it will also be yellow because "yellow" is dominant. The "green" trait, although present, remains hidden because it is recessive. It can, however, reappear in future generations (Griffiths et al., 2012).

Therefore, every organism carries two copies of each gene (one from each parent), and these gene copies are known as alleles. These alleles can be the same (homologous) or different (heterologous). When they are heterologous, one allele may express itself more strongly than the other, leading to the concepts of dominant and recessive traits (Griffiths et al., 2012). A dominant trait is the one that appears in the organism even if there is only one copy of the gene associated with that trait. In other words, if an organism has two different alleles, and one is dominant, the phenotype (or physical expression) will be determined by the dominant allele. For example, in humans, having free earlobes is a dominant trait. If you have a "free earlobe" allele from one parent and an "attached earlobe" allele from the other parent, you will have free earlobes because the free earlobe trait is dominant (Griffiths et al., 2012). On the other hand, a recessive trait is one that only appears when an organism has two copies of the gene associated with that trait. If there is a dominant allele present, the recessive trait will not show. Using the previous example, the individual would only have attached earlobes (the recessive trait) if they received the "attached earlobe" allele from both parents (Griffiths et al., 2012). It is crucial to remember that "dominant" does not mean "better" or "more common". These terms only describe how traits are expressed, not their value or frequency in the population. Also, while Mendel's laws and the concept of dominant and recessive traits work well for many traits, there are exceptions. Many traits are controlled by multiple genes and exhibit a range of phenotypes, like human height and skin color. Other traits can be influenced by environmental factors, or display co-dominance or incomplete dominance (Pierce, 2012).

Figure 4: Mendel's law of segregation (ThoughtCo, n.d.).

Mendel's Second Law, the Law of Independent Assortment, explains how different traits are inherited independently of each other. So, inheriting a certain eye color does not directly affect inheriting a certain height. Using his peas again, Mendel noticed that a pea plant with yellow peas was not necessarily more likely to be tall, these traits are assorted independently in offspring. However, there is a caveat: genes located close together on the same chromosome can often be inherited together due to a phenomenon called linkage. But overall, Mendel's Second Law provides a fundamental understanding of how traits are inherited independently (Pierce, 2012).

Another principle in genetics is codominance and incomplete dominance. These two concepts explain situations where dominance and recessiveness are not so clear-cut. Codominance occurs when both alleles of a gene are expressed simultaneously in a heterozygote, an individual with two different alleles for a particular trait. Think of it like both genes having an equal say in the outcome. An example is the AB blood type in humans, where both the A and B alleles are expressed (Alberts et al., 2007). On the other hand, incomplete dominance is when a heterozygote shows a trait that's somewhere in the middle of the two parent traits. Neither allele is dominant, so they blend. For instance, if a red flower and a white flower mate, the offspring might have pink flowers, which is an intermediate color (Alberts et al., 2007). Genetics is filled with more complex concepts and exceptions to these rules, but Mendel's laws and these additional principles provide a solid foundation for understanding how traits are inherited.

Figure 5: Google's tribute image for Mendel's 189th anniversary (The Guardian, n.d.).

Mendel's Laws revolutionized how we understand inheritance. By looking at pea plants, Mendel introduced a way to predict the traits of offspring based on the traits of the parents. Today, his laws continue to guide research and applications in fields such as human medicine, agriculture, and conservation biology. Despite his significant work, Mendel's findings were initially overlooked by the scientific community. Today, Mendel's Laws of Inheritance form the bedrock of genetics. They are applied in various fields, from human medicine, where they help us understand diseases passed down in families, to agriculture, where they guide the breeding of plants and animals with desirable traits. Mendel's legacy thus remains integral to our understanding of life's diversity.

Polygenic Inheritance

The term "polygenic" can be broken down into "poly-", which means many, and "-genic," which refers to genes. Therefore, polygenic inheritance revolves around the idea that multiple genes, often dispersed across various chromosomes, can influence a single trait. Each of these genes usually has a small effect, but together they can produce a wide variety of phenotypes (observable traits). This kind of inheritance results in what we call a continuous distribution of traits, leading to a spectrum rather than distinct categories (Pierce, 2012).

Figure 6: Height inheritance is influenced by multiple genes (NPR, n.d.).

In polygenic traits, the alleles often have an additive effect. That means the total phenotypic value of the trait in a given individual is roughly the sum of the effects of all the involved alleles. For instance, for a hypothetical trait controlled by three genes, if each dominant allele adds one "unit" to the trait, an individual with six dominant alleles would have a value of six units for that trait, while someone with none would have a value of zero (Griffiths et al., 2012).

Traits that can be measured and exist along a continuum, like height or skin color, are often referred to as quantitative traits. Scientists use a method called Quantitative Trait Loci (QTL) mapping to locate the positions of genes that affect these traits. A QTL is a segment of DNA (often a gene or group of genes) that is correlated with variation in a quantitative trait. This location can be pinpointed on a chromosome. QTLs are especially significant in understanding how multiple genes can influence a trait. Essentially, when researchers identify a QTL, they are finding a specific location in the DNA that is associated with variations in a particular trait(Griffiths et al., 2012). QTL mapping is a statistical method used to locate and estimate the effect of genes on quantitative traits.

The process consists of:

• Crossbreeding: Start with two strains or species that have distinct phenotypes for the trait in question. Crossbreed these to produce a generation of offspring.

• Phenotypic Measurement: Measure the trait of interest in each offspring.

• Genotyping: Obtain genetic markers, which are specific DNA sequences that can vary among individuals, for each offspring. These markers span across the genome.

• Statistical Analysis: Using statistical methods, researchers determine which markers correlate with variations in the trait. If a marker correlates strongly with a trait, a QTL is likely nearby (Pierce, 2012).

Figure 7: Quantitative Trait Locus (QTL) Identification (Quantitative Trait Locus (QTL) Identification, n.d.).

By studying the genomes of individuals at the extreme ends of the distribution (very tall versus very short, for instance), researchers can pinpoint locations on chromosomes that harbor genes affecting the trait (Pierce, 2012). Environmental factors can also play a pivotal role in the expression of polygenic traits. For instance, two plants might have genetic potentials to grow to similar heights, but if one receives more sunlight or water, it could end up taller. Similarly, humans with genetic predispositions to be tall might not reach their potential height due to malnutrition during childhood (Griffiths et al., 2012).

Many common diseases, such as diabetes, hypertension, and many psychiatric disorders, are polygenic. This means that no single gene causes the disease; instead, small contributions from many genes increase the risk. In modern medicine, there is a growing interest in calculating polygenic risk scores for individuals. This approach involves tallying up the effects of many risk-increasing variants across the genome to predict an individual's susceptibility to certain diseases (Pierce, 2012).

Figure 8: Illustration of the mechanism of Diabetes at cellular level (Fine Art America, n.d.).

For example, Type 2 diabetes (T2D) is a chronic condition that affects how the body metabolizes glucose, its primary source of energy. While lifestyle factors like diet and exercise play a significant role in the development of T2D, genetics also contribute, and the genetic underpinnings of T2D are complex. It is not just one gene, but multiple genes that interact and increase susceptibility to the disease (Pierce, 2012). Over the years, genome-wide association studies (GWAS) have been employed to identify numerous genetic loci associated with an increased risk of developing T2D. These loci often represent regions with multiple genes, complicating the task of pinpointing exact causative genes. Some of the genes implicated are involved in insulin production, glucose metabolism, and pancreatic β-cell function (McCarthy, 2010). What makes T2D fascinating (and challenging) is the interplay between genetics and the environment. For instance, carrying risk alleles for T2D does not guarantee the onset of the disease. However, when combined with lifestyle factors like a high-calorie diet, lack of exercise, and obesity, the risk substantially increases. These environmental influences can act as triggers in genetically predisposed individuals (Alberts et al., 2014). Given the multiple genetic markers associated with T2D, there's a growing interest in developing polygenic risk scores (PRS) for the disease. A PRS aggregates the small risk increments from various genetic loci to generate an individual's overall genetic risk. While not yet a standard tool in clinical settings, PRS for T2D can potentially help in identifying individuals at high risk and guiding preventive measures (Mahajan et al., 2018). Understanding the polygenic nature of T2D has implications for treatment and prevention. Recognizing that different individuals may have varying genetic susceptibilities can pave the way for personalized medicine approaches, tailoring interventions based on an individual's unique genetic makeup. However, it also underscores the importance of public health measures, given that lifestyle modifications can significantly mitigate genetic risks (McCarthy, 2010).

Polygenic traits have interesting implications for evolution. Because there are many genes involved, and each contributes a small amount to the trait, these traits can evolve gradually, with populations shifting in one direction or another based on the changing frequencies of contributing alleles. This nuanced, multi-genic structure allows for more fluid adaptation to environmental changes (Alberts et al., 2007). Polygenic inheritance adds layers of complexity to genetics. The vast combinations of alleles and the influence of environmental factors ensure a rich diversity of traits, highlighting the intricate interplay of genes in shaping organisms.

Inheritance Patterns

The expression "inheritance patterns" refers to the typical routes our traits or characteristics (like our height, eye color, or certain health conditions) take as they are passed from parents to children. Understanding these patterns allows for the prediction and interpretation of the myriad ways traits and conditions can be passed through generations.

Figure 9: Mendelian Inheritance (Science Photo Library, n.d.).

As previously discussed, in Dominant Inheritance, you might find a family where a single parent's trait, such as curly hair, gets passed on to their children even if the other parent has straight hair. That's because the curly hair trait "overpowers" the straight hair one. One classic example is Huntington's disease, a neurodegenerative disorder. If a parent has the gene for this condition, their child has a 50% chance of inheriting and manifesting the disease (Pierce, 2012). On the other hand, with Recessive Inheritance, both parents might secretly carry a characteristic without showing it. For example, if both parents unknowingly have the trait for blue eyes hidden away, their child could unexpectedly end up with blue eyes (Pierce, 2012). Cystic fibrosis is a recessive genetic disorder. Both parents need to pass on the faulty gene for their child to develop the condition (Pierce, 2012).

In addition there are traits tied to our gender chromosomes, labeled as X and Y. Females have two Xs, and males have an X and a Y. In X-linked Dominant Inheritance, a girl can show a trait if it appears on just one of her X chromosomes. For males, since they have only one X, if that X carries the trait, it will manifest. Rett syndrome, a neurodevelopmental disorder, is predominantly observed in females because they can survive with one mutated X chromosome. Males usually do not survive infancy with the mutation (Pierce, 2012). Meanwhile, in X-linked Recessive Inheritance, males are more likely to show a trait because they have just one X. For a female to display this trait, it needs to be on both of her X chromosomes. Haemophilia, a blood-clotting disorder, is more commonly observed in males, if a male inherits the faulty gene on his X chromosome, he'll have the condition (Pierce, 2012).

Figure 10: Sex-linked Ineritance (Sex-Linked Traits and X Inheritance According to Modern Genetics, n.d.).

There is also Y-linked Inheritance, where traits are tied exclusively to the Y chromosome. This means only males can display these traits, and fathers will inevitably pass these specific characteristics down to all their sons (Pierce, 2012). Certain types of male infertility can be traced back to mutations on the Y chromosome as it is passed directly from father to son (Pierce, 2012). A special category is Mitochondrial Inheritance. Here, DNA from our mitochondria—tiny structures inside our cells responsible for producing energy—dictates the trait, with the unique aspect being that only mothers pass these traits onto their offspring, regardless of sex. Leber's hereditary optic neuropathy (LHON) is a condition that leads to vision loss, inherited through mitochondrial DNA (Pierce, 2012). Another interesting type is Codominant Inheritance. For instance, when considering blood types, if one parent passes down a blood type "A" trait and the other a "B", their child inherits both, resulting in blood type "AB".

Conclusion

The fascinating world of genetics unravels the intricate tapestry that makes each individual unique. Genetic variations underpin the vast array of differences in appearance, behavior, and susceptibility to diseases among human beings. From the color of individual's eyes to preferences for taste and sleep patterns, genes act as the architects of physical and behavioral traits.

Figure 11: The intricate mechanisms of inheritance (iStock, n.d.).

Gregor Mendel's groundbreaking work with pea plants laid the foundation for our understanding of inheritance patterns, unveiling the fundamental laws of segregation and independent assortment. His discoveries revolutionized our comprehension of how traits are passed from one generation to the next and continue to guide research and applications in various fields to this day. Polygenic inheritance, with its additive effect of multiple genes contributing to a single trait, paints a picture of continuous distribution and infinite possibilities. This dynamic process highlights the complexities of gene interactions and environmental influences in shaping human traits and characteristics. This exploration tackled how genetic variations play a pivotal role in the development of diseases. Some conditions arise from single gene mutations, while others stem from the intricate interplay of multiple genes and environmental triggers. The study of genetics allows us to gain insights into the origins of diseases and provides avenues for personalized medicine approaches, tailoring interventions based on an individual's unique genetic makeup.

Understanding the various inheritance patterns, from dominant and recessive traits to X-linked and mitochondrial inheritance, enhances our knowledge of how traits are transmitted across generations. The interplay of genes and environmental factors contributes to the profound diversity and intricacy observed in human beings. As researchers continue to unravel the mysteries of genetics, their understanding of human variation and health will expand. Advancements in genetic research hold the promise of unlocking new treatments, interventions, and preventive measures for a wide range of diseases and conditions. In conclusion, genetic variations lie at the core of what makes us who we are. From the contributions of Mendel's peas to the complex interactions of polygenic traits and various inheritance patterns, genetics continues to be a captivating frontier of exploration. Embracing this understanding enriches appreciation of the diversity of life and inspires further advancements in the field of genetics, ultimately contributing to the improvement of human health and well-being.

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