Principle Of Genetics

[Boyan Atanaschev]

In1908, two scientists, Godfrey H. Hardy, an English mathematician, and Wilhelm Weinberg, a German physician, independently worked out a mathematical relationship that related genotypes to allele frequencies.05

Their mathematical concept, called the Hardy-Weinberg principle, is a crucial concept in population genetics. It predicts how gene frequencies will be inherited from generation to generation given a specific set of assumptions.06 The Hardy-Weinberg principle states that in a large randomly breeding population, allelic frequencies will remain the same from generation to generation assuming that there is no mutation, gene migration, selection, or genetic drift.04 This principle is important because it gives biologists a standard from which to measure changes in allele frequency in a population.

To illustrate how the Hardy-Weinberg principle works, let us consider the MN blood group. Humans inherit either the M or the N antigen, which is determined by different alleles at the same gene locus. If we let the frequency of allele M=p and the frequency of the other allele N=q, then the next generation's genotypes will occur as follows:

Suppose that scientists are observing a population of lab-bred flies, and discover a gene controlling eye color. The R allele produces regular-colored eye pigment, while the r allele produces red pigment. Individuals that are heterozygous (Rr) have pink eyes. In a population of 150 flies, 15 flies have red eyes, 90 have normal eye color, and 45 have pink eyes.

In order for a population to be considered to be in equilibrium, it must remain the same from generation to generation. Therefore, in order to determine if this population of fruit flies is in Hardy-Weinberg equilibrium, the genetic distribution of the current generation must be compared to a prediction of the genetic distribution of the next generation, as calculated using the Hardy-Weinberg equation.

Comparing the expected numbers with the actual numbers of each phenotype, population geneticists can determine if populations are either in equilibrium (or very close to it) or are experiencing disequilibrium of some sort. In this example:

In this example, the population is not in equilibrium since the expected and observed values do not match. Once a population geneticist determines that a population is in disequilibrium, the reasons can be explored. Disequilibrium can be attributed to different possible mechanisms, depending on (1) the context of the population, and (2) the manner in which the population is skewed.

When a population meets all of the of the Hardy-Weinberg conditions, it is said to be in Hardy-Weinberg equilibrium (HWE). Human populations do not meet all of the conditions of HWE exactly, and their allele frequencies will change from one generation to the next and the population will evolve. How far a population deviates from HWE can be measured using the "goodness of fit" or chi-squared test (χ2).

Since we have two alleles, we therefore have 3 minus 1, or 2 degree of freedom. Degrees of freedom is a complex issue, but we could look at this in simple terms: if we have frequencies for three genotypes that are truly representative of the population then, no matter what we calculate for two of them, the frequency of the third must not be significantly different for what is required to fit the population.

Looking across the distribution table for 2 degrees of freedom, we find our chi-squared value of 4.221 is less than that required to satisfy the hypothesis that the differences in the O and E data did not arise by chance. Since the chi-squared value falls below the 0.05 (5%) significance cutoff, we can conclude that the Forensics Town population does not differ significantly from what we would expect for Hardy-Weinberg equilibrium of the MN blood group.

ThePrinciple of Segregation describes how pairs of gene variants are separatedinto reproductive cells. The segregation of gene variants, called alleles, andtheir corresponding traits was first observed by Gregor Mendel in 1865. Mendelwas studying genetics by performing mating crosses in pea plants. He crossedtwo heterozygous pea plants, which means that each plant had two differentalleles at a particular genetic position. He discovered that the traits in theoffspring of his crosses did not always match the traits in the parentalplants. This meant that the pair of alleles encoding the traits in eachparental plant had separated or segregated from one another during theformation of the reproductive cells. From his data, Mendel formulated thePrinciple of Segregation. We now know that the segregation of genes occursduring meiosis in eukaryotes, which is a process that produces reproductivecells called gametes.

Avery, MacLeod and McCarty identified DNA as the "transforming principle" while studying Streptococcus pneumoniae, bacteria that can cause pneumonia. The bacteriologists were interested in the difference between two strains of Streptococci that Frederick Griffith had identified in 1923: one, the S (smooth) strain, has a polysaccharide coat and produces smooth, shiny colonies on a lab plate; the other, the R (rough) strain, lacks the coat and produces colonies that look rough and irregular. The relatively harmless R strain lacks an enzyme needed to make the capsule found in the virulent S strain.

Griffith had discovered that he could convert the R strain into the virulent S strain. After he injected mice with R strain cells and, simultaneously, with heat-killed cells of the S strain, the mice developed pneumonia and died. In their blood, Griffith found live bacteria of the deadly S type. The S strain extract somehow had "transformed" the R strain bacteria to S form. Avery and members of his lab studied transformation in fits and starts over the next 15 years. In the early 1940s, they began a concerted effort to purify the "transforming principle" and understand its chemical nature.

Bacteriologists suspected the transforming factor was some kind of protein. The transforming principle could be precipitated with alcohol, which showed that it was not a carbohydrate like the polysaccharide coat itself. But Avery and McCarty observed that proteases - enzymes that degrade proteins - did not destroy the transforming principle. Neither did lipases - enzymes that digest lipids. They found that the transforming substance was rich in nucleic acids, but ribonuclease, which digests RNA, did not inactivate the substance. They also found that the transforming principle had a high molecular weight. They had isolated DNA. This was the agent that could produce an enduring, heritable change in an organism.

Until then, biochemists had assumed that deoxyribonucleic acid was a relatively unimportant, structural chemical in chromosomes and that proteins, with their greater chemical complexity, transmitted genetic traits.

Genetic Alliance; The New York-Mid-Atlantic Consortium for Genetic and Newborn Screening Services. Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2009 Jul 8.

We are hopeful that these principles will help determine the content for lectures,workshops, seminars, and complete courses. We leave it to individual professionals, whoknow their audiences and the context of the instruction in genetics, to select theapplicable principles, determine the examples selected to illustrate those principles,and define the level of detail appropriate for the audience in question.

The Principles in Genetics and Epigenetics (PIGE) class is designed for students who have a major interest in the aspects of experimental and human genetics and epigenetics as they relate to human disease, including Mendelian disorders, complex diseases and cancer. Students are required to have completed the core course (or equivalent). This class will provide in-depth instruction in four areas: 1) Experimental genetics, 2) Human genetics, 3) Epigenetics, 4) Applied bioinformatics. The class will be held two times a week for one and a half hours. Students are expected to actively participate in the course by initiating discussions, asking questions, and providing constructive comments, as well as completing weekly homework assignments based on the material covered in the lectures of the preceding week. Students will be evaluated by attendance, participation, bioinformatics workshop participation and completion of assigned exercises, and overall performance on the assigned homework. As a foundational course, this course is designed to introduce students to the basic principles in genetics and epigenetics and prepare the student to generate novel hypothesis-driven projects as part of their own research in the areas of genetics and epigenetics inside and outside of G&E laboratories. The course emphasizes active learning through a combination of didactic lectures, selected application lectures and a bioinformatics workshop. Auditing this course is permitted with Course Directors' approval.

Groundbreaking research on the universality and diversity of microorganisms is now challenging the life sciences to upgrade fundamental theories that once seemed untouchable. To fully appreciate the change that the field is now undergoing, one has to place the epochs and foundational principles of Darwin, Mendel, and the modern synthesis in light of the current advances that are enabling a new vision for the central importance of microbiology. Animals and plants are no longer heralded as autonomous entities but rather as biomolecular networks composed of the host plus its associated microbes, i.e., "holobionts." As such, their collective genomes forge a "hologenome," and models of animal and plant biology that do not account for these intergenomic associations are incomplete. Here, we integrate these concepts into historical and contemporary visions of biology and summarize a predictive and refutable framework for their evaluation. Specifically, we present ten principles that clarify and append what these concepts are and are not, explain how they both support and extend existing theory in the life sciences, and discuss their potential ramifications for the multifaceted approaches of zoology and botany. We anticipate that the conceptual and evidence-based foundation provided in this essay will serve as a roadmap for hypothesis-driven, experimentally validated research on holobionts and their hologenomes, thereby catalyzing the continued fusion of biology's subdisciplines. At a time when symbiotic microbes are recognized as fundamental to all aspects of animal and plant biology, the holobiont and hologenome concepts afford a holistic view of biological complexity that is consistent with the generally reductionist approaches of biology.

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