Introduction to Genetics

• The presentation is about the field of genetics.
• Genetics was initially of interest because it provided answers about life's origins and how the passing of traits occurred.

What is Genetics

• Genetics comes from the Ancient Greek word Genesis, and is translated as origin, formation, creation.
• Genetics is a scientific field that studies genes, variations, and heredity, studying eye and hair color, and blood groups.
• It studies how traits pass from parents to offspring.
• Genetics is a multidisciplinary science working with biology, chemistry, physics, and computer technology.

History of Genetics

• Genetics is considered a new science division.
• Many philosophers like Pythagoras, Hippocrates, Aristotle, and Epicurus contributed to genetics science in medieval times.
• Many theories, like abiogenesis, preformation, and epigenesis were proposed before the scientific revolution.

Mendel, The Father of Genetics

• Modern genetics began with the work of Gregor Mendel on pea plants.
• Between 1856 and 1863 he performed hybridization experiments with pea plants, publishing results in 1866 (Experiments in Plant Hybrids).
• His work was not understood by the scientific community at the time.
• Mendel's studies were rediscovered about 30 years later.

After Mendel

• Friedrich Miescher isolated nucleic acids from white blood cells in 1869, and identified the chemical structure of nucleic acids in 1871.
• Walter Flemming who lived from 1843-1905, identified cell division process in 1882.
• Theodor Boveri who lived from 1862-1914, pointed out the relation between chromosomes and inheritance.
• Chromosomes are double-stranded DNA and associated histone proteins, and are condensed from of DNA by histone proteins.
• William Bateson, who lived from 1861-1926, termed genetics in 1909.
• Wilhelm Johannsen, who lived from 1857-1927, described genes as the fundamental unit of heritable phenotypic traits in 1909.
• Thomas Hunt Morgan, who lived from 1866-1945, determined that genes are on the chromosomes in 1910.
• Scientists later studied which material in cells serves as genetic material, and Frederick Griffith worked on this in 1928.
• Avery, MacLeod and McCarty contributed to the understanding of genetic material in 1944.
• Hershey and Chase helped advance the understanding of genetic material in 1952.

Identification of DNA

• In 1928, Frederick Griffith formed a basis to prove that DNA was a genetic material.
• Frederick Griffith experimented with 2 strains of Diplococcus pneumoniae.
• The IIIS strain (virulent) has a polysaccharide capsule, to produce smooth colonies.
• The IIR strain (avirulent) does not have a capsule, and produces rough colonies.
• In Griffith's conclusions, something from the dead type IIIS bacteria transformed type IIR into type IIIS bacteria.
• This process was called transformation.

Avery, MacLeod and McCarty Experiments

• There are 4 categories of biomolecules in the cells: Nucleic acids, Proteins, Carbohydrates, Lipids.
• Each of these biomolecules were candidates to be genetic material.
• In 1944 Avery, MacLeod and McCarty used enzymes to hydrolyze these molecules.
• The scientists homogenized and filtered virulent IIIS type bacteria to obtain a mixture of proteins, lipids, DNA, RNA and carbohydrates, dividing the mixture into 5 tubes.
• Each tube had one of the enzymes that hydrolyze a biomolecule.
• The mixtures were then mixed with avirulent IIR type bacteria.
• After cultivation, IIR type bacteria were injected into the mice.
• They observed that only the mouse injected with DNaz enzyme containing mixture, was alive.
• The scientists concluded that DNA is genetic material.

Hershey and Chase Experiments

• Hershey and Chase confirmed that DNA is genetic material, utilizing T2 phage(a virus) and radioisotopes of phosphorus and sulphur.
• Phosphorus exist in DNA, while sulphur exists in proteins.
• They marked DNA and proteins with radioisotopes of phosphorus and sulphur.
• The scientists used radioisotopes of phosphorus and sulphur to distinguish DNA from proteins.
• The radioisotope 32P labels DNA specifically.
• The radioisotope 35S labels protein specifically.
• Non-radioactive E. coli were infected with radioactively-labeled phages, before the phage coats were removed from the cells.
• Determining if 32P or 35S was inside bacteria was the goal.

Discovery of DNA Structure

• After it was understood that DNA was the genetic material, scientists studied to identify the structure of DNA.
• Erwin Chargaff of 1952, Rasalind Elsie Franklind of 1952, and Watson and Crick of 1953, all contributed.
• Chargaff worked on base concentrations in DNA from 1949-1951, finding; The quantity of purine and pyrimidine is equal (A+G=C+T).
• Adenine amount is equal with thymine, while guanine amount is equal with cytosine (A=T and G=C).
• The amount of A+T do not have to be equal with G+C.
• Elsie Franklin worked on X-ray diffraction.
• With this method they could take X-ray photographs of DNA between 1951-1953, helping to understand DNA's double helix structure.
• The structure of DNA was discovered in 1953.
• When Watson and Crick used Franklind, Wilkins, and Chargaff's data, they suggested the double helix model of DNA.
• They were awarded with the Nobel Prize in 1962.
• Watson and Crick described DNA as a double helix, containing two long, helical strands wound together.
• In their model, each DNA strand contained individual units called bases, where the bases along one DNA strand matched the bases along the other DNA strand.
• Another type of nucleic acid, mRNA, was discovered in 1961.

Modification of DNA

• Together with Kent W. Wilcox, Smith discovered restriction enzymes in 1970.
• Isolation and characterization of these enzymes allowed for the creation of recombinant DNA molecules.
• Transgenic organisms have a gene from another organism, do not naturally exist, and are produced in laboratuvar conditions.

What is Genetics?

• Genetics is a multidisciplinary science that studies genes, variations, and heredity in organisms, and is related to cells, organisms and their offspring, and populations.
• DNA, or Deoxyribonucleic acid, is the genetic material of all organisms.
• DNA is a nucleic acid.
• Nucleic acids are polymeric macromolecules.
• Units of these macromolecules are nucleotides.

Function of Genetic Material

• Genetic material must contain the information necessary to construct an entire organism.
• Genetic material can be passed from parent to offspring.
• Genetic material must be accurately copied.
• Genetic material must have diversity as is found in the innumerable forms of life.
• A gene is a molecular unit of living organisms and is usually a DNA fragment, but can also be RNA in viruses.
• Genes hold the information and encode proteins needed for biological processes, to build and maintain an organism's life.
• Genes in eukaryotic cells are found in the nucleous along the chromosome, where's genes in prokaryotic cells are found in the nucleoid free within the cytoplasm.

Structure of Genes

• A gene contains a promoter, which is a regulatory region that initiates transcription of a gene and locates near the transcription start sites.
• Coding region, has codes for protein synthesis.
• Termination site (stop), has some marks to terminate of a gene transcription.
• DNA only carries information; it cannot directly perform the actions that occur in a cell, and transcribes RNA, which is translated into proteins.

Epigenetics

• All of our cells are produced from one single cell (zygote).
• In early embryonic development, certain genes in cells are silenced.
• Each cell type has different active genes.
• Every cell has a unique protein content.
• For example, epithelial cells do not need insulin hormone, so the genes that are responsible for insulin production are inactivated.
• Genes are inactivated through a complex process, where the location of the gene being inactivated is packaged with histone proteins.
• These packaged parts of DNA are called heterochromatin, and genes in the heterochromatin cannot be expressed.
• The less intense part of the DNA is named euchromatin, and the genes in euchromatin are active.

Mendel's Experimental Approach

• Mendel choose a good model organism in the pea plant, because it has a short life cycle, and matures in a season.
• Pea plants are also easy to grow, easy to create hybrids, and have many phenotypic differences.
• Many seeds can be obtained from one plant, which is needed for reliability of statistical data.
• He chose seven easily detectable phenotypic traits passed down to successive generations; flower color (purple, white), flower position (axial, terminal), seed pod color (green, yellow), seed pod shape (inflated, constricted), seed color (yellow, green), seed shape (round, wrinkled), plant height (tall, dwarf).
• Mendel only studied one or a few numbers of characters in every hybridization (purple flower X white flower/monohybrid) or tall plant with yellow X dwarf pant with green seed/dihybrid.
• He recorded every quantitative result from hybridization experiments, which is needed for a good statistical analysis to obtain a ratio.
• Mendel established many rules of heredity.

Mendel Experiment Example

• In the first example, purple flowers are dominant (WW) and white flowers are recessive (ww).
• The F1 generation are all Ww, meaning the flowers are all purple.
• With F1 self crosses, one is WW, two are Ww, and one is ww.
• This means that out of the four outcomes, three are purple and one is white.

Mendel's Rules

• Mendel proposed four principles of heredity.
• Paired Factors: Genetic characters are controlled by some factors that exist as two copies (paired) in an organism.
• Dominant and Recessive: Paired factors, responsible from one character, can result different phenotypes, with one factor being dominant.
• Independent Segregation: During gamete formation paired factors of a gene randomly segregate, so each gamete have one of these factors in equal ratio.
• Independent Assortment: During gamete formation paired factors of different genes are inherited independently of another one.
• All diploid organisms have two sets of chromosomes, with n=14 in peas, with one set inherited maternally and the other paternally.
• In every chromosome set, there are genes with different alleles.
• Different alleles of a certain gene can be expressed unequally.
• An allele has more impact in phenotype called dominant.

Non-Mendelian Inheritance

• Today certain characters does not obey the Mendelian principles; they may exhibit linkage genes, or incomplete dominance, or codominance.
• Multiple alleles, sex chromosome inheritance, epistasis, genetic complementation, pleiotropy, and polygenic inheritance, are also non-Mendelian traits.

Incomplete Dominance

• Opposite alleles of the same genes are not dominant or recessive, sometimes causing an intermediate phenotype not similar to both parents.

Codominance

• Both alleles of a gene can be expressed, resulting in two proteins.
• We can observe both phenotypes at the same time.
• MN blood type is an example for codominance, and was defined by K. Landsteiner and P. Levin.
• Glycoprotein on red blood cells is encoded by a gene located at the fourth chromosome.
• In human this protein have two forms (MN).

Multiple Alleles

• A diploid organism can have two alleles of a gene.
• In the population, there are many alternative of gene forms.
• Multiple alleles can only be studied in the populations, and the best example is ABO blood type carbohydrate antigens.
• The gene of this protein is located at ninth chromosome, and has three alternative forms (alleles).
• An individual can have one of six possible genotypes (IAIA, IAIO, IBIB, IBIO, IAIB, IOIO).
• These genotypes cause four phenotypes (A, B, AB, O).
• There is no standard phenotypic ratio for ABO blood type, because different crosses give different phenotype ratio.

Inheritance With Sex Chromosomes

• In many animals and some plants, one gender (male or female) has a different chromosome pair responsible for sex.
• In human (2n=46) these are X and Y chromosomes.
• Both genders have 22 autosomal chromosome pairs.
• Females have XX sex chromosomes while males have XY.
• Genes located at X chromosomes, can't be homozygote or heterozygote in males.
• Males just have one X chromosome.
• These genes are hemizygote and there is no alternative allele also no dominance.
• Daltonizm, hemophilia, and Hunter syndrome are examples for X-linkage traits.

Epistasis

• There are inheritance mechanisms where multiple alleles and incomplete dominance is about the interaction between alleles of the same gene.
• Different genes can also affect each other.
• Epistasis is the term that refers to the action of one gene upon another, where one gene can repress another gene.

Genetic Complementation

• Genetic complementation is when two genes are responsible from the same character, but none of them can show its phenotype without the other.
• For multiple alleles, A and B genes are responsible from purple flower color.
• Dominant alleles of both genes have to be together for purple flowers, otherwise flowers will be white.
• Possible combinations are AaBb (purple), Aabb(White), or aaBB(White).

Pleiotropy

• Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits.
• One gene influences multiple phenotypic traits.

Polygenic Inheritance

• A trait that is determined by several genes and can show continuous variation within a population.
• Eye, hair, and skin color are examples of polygenic traits.
• Height is a good example of a polygenic trait because within a given population, there can be a wide range of continuous differences

Penetrance

• Penetrance refers to the probability of a gene or trait being expressed.
• In some cases, despite the presence of a dominant allele, a phenotype may not be present.
• One example of this is polydactyly in humans (extra fingers and/or toes).
• A dominant allele causes polydactyly in humans, but not all humans who have the allele display the extra finger.
• If 80% of the people who inherit this dominant allele have an extra finger, it is said that the penetrance of this allele is 80%.

Expressivity

• Expressivity on the other hand refers to variation in phenotypic expression when an allele is penetrant.
• Back to the polydactyly example, an extra finger can be full size or just a stub.
• Hence, this allele has reduced penetrance as well as variable expressivity.
• Variable expressivity refers to the range of signs and symptoms that can occur in different people with the same genetic condition.

Cytoplasmic Inheritance

• Genetic studies showed that Mendelian type of inheritance is not always true.
• Other inheritance mechanisms can't be explained by Mendel rules.
• Codominance, incomplate dominance, and multiple allels, are only some example of them.
• These certain types of inheritance are still interested with nuclear genes, as known genes are DNA fragments and most percentages of our DNA is located in the nucleus.
• Cytoplasm of a cell also has DNA fragments, the genetic material of an organelle or free cytoplasmic DNA that inserted into cell via viruses.
• Another type of cytoplasmic inheritance is mediated by proteins that reserved in egg cell.

Three Maternal Inheritance Mechanisms

• The three inheritance mechanisms are maternal, and do not include a nuclear genome, and are called extra nuclear inheritances.
• Inheritance with organelle/mitochondria and chloroplast, or inheritance with viruses, as well maternal effect.
• The first and second mechanisms are still mediated with DNA, but with extra nuclear DNA, and the last one is mediated by proteins.
• Mitochondria and chloroplast are two organelle that have their own DNA.
• This means that all mitochondria (in animals and plants) and chloroplast (in plants) are inherited from mother to the offspring.
• If egg donor have a mutation which causes a disease at DNA of mitochondria/chloroplast, this mutation will be inherited to all offsprings.
• In CO2 sensitive female X normal male, all fruit fly are sensitive.
• In normal female X CO2 sensitive male, all fruit fly are normal.
• This last type of cytoplasmic inheritance/maternal effect, is not mediated by gene.
• During egg formation some proteins are produced and reserved in cytoplasm.
• An example of this maternal effect type of inheritance, is Shell shape of Limnaea peregra.
• Limnaea is a hermaphrodite snail.
• The gene that determines the Shell shape have two alleles.
• The D allele causes dextral (right side) type and d sinistral (left side), where (D) is dominant to (d).
• This gene is expressed proteins and these proteins are reserved in egg cell.