Genetics: The Scienceof Heredity1.- Introduction2.- Mendelian genetics3.- Chromosomal theory of inheritance4.- Mutations5.- Human Inheritance

Cell division

Cell divisionAll cells are derived from preexisting cells.Cell division is the process by wich cells produce new

cells.

Reasons for cell divisionCell growthRepair and replacement of damaged cell parts: some

tissues must be repaired often such as the lining of gut, white blood cells, skin cells with a short lifespan. Othercells do not divide at all after birth such as muscle andnerve.

Reproduction of the species.

Cell CycleDuring a cell’s life cycle there are various different phases. The Cell Cycle includes two main parts:

Interphase: is the longest part of a cell’s life cycle and is called “the resting stage” because the cell isn´t dividing. during interphase. During interphase cell grows, develops, makes a copy of its DNA, prepares to divide into two cells and carry on all their normal metabolicfunctions.

Cell division: includes Mitosis (nuclear division) andCytokinesis (division of the cytoplasm).

Structure of DNADeoxyribonucleic Acid (DNA) is a double-stranded, helical molecule consisting of two sugar-phosphatebackbones on the outside, held together by hydrogenbonds between pairs of nitrogenous bases on the inside. The bases are of four types (A, C, G & T): pairing alwaysoccurs between A & T and C & G (complementary base pairing). This structure was first described by James Watson and Francis Crick in 1953.

DNA (The Double Helix)

Sugar-phosphatebackbone Base

Phosphate

Sugar

Hydrogen bonds

A: adenineC: cytosineG: guanineT: thymine

Watson & Crick

Replication of DNASince the instructions for making cell parts are encoded in the DNA, each new cell must get a complete set of theDNA molecules. This required that the DNA be copied(replicated, duplicated) before cell division. This processtakes place during the Interphase stage of the Cell Cycle.

Each strand of the original molecule acts as a template forthe synthesis of a new complementary DNA molecule. The two strands of the double helix are first separated by enzymes. With the assistance of other enzymes, spareparts aivalable inside the cell are bound to the individual strands following the rules of complementary base pairing : adenine (A) to thymine (T) and guanine (G) tocytosine C. Finally, two strands of DNA are obtained fromone, having produced two daughter molecules which are identical to one another and to the parent molecule.

MITOSISMitosis is the process by which somatic cells divide andmultiply. It results in the production of two daughter cellsfrom a single parent cell. The two daughter cells are identical to one another and to the original parent cell. In a typical animal cell, mitosis can be divided into fourprincipal stages:

Prophase: The chromatin, diffuse in interphase, condenses to form double-rod structures calledchromosomes. Each chromosome has duplicated andnow consists of two sister chromatids (the two rods). Each chromatid in a chromosome is an exact copy of theother. The two chromatids are held together by a structurecalled centromere. At the end of the prophase, thenuclear envelope breaks down.

Metaphase: The chromosomes align at the equatorialplate and are held in place by microtubules attached tothe mitotic spindle and to part of the centromere.

Anaphase: The centromere divide. Sister chromatidsseparate and move toward the corresponding poles.

Telophase: Daughter chromosomes arrive at the polesand the microtubules dissapear. The condensedchromatin expands and the nuclear envelope reappears.

Cytokinesis: The cytoplasm divides, the cell membranepinches inward ultimately producing two daughter cells.

Centromere Sister Chromatids

Mitosis phases as seen with microscope

Prophase Anaphase

Metaphase Telophase

MEIOSIS

Meiosis is a type of cell division by which sex cells (eggs and sperm) are produced. Is the process by which a single parent diploid cell (bothhomologous chromosomes) divides to produce four daughter haploidscells (one homologous chromosome of the pair). Meiosis involves a reduction in the amount of genetic material. It comprises two successivenuclear divisions with only one round of DNA replication. Four stages can be described for each nuclear division:

Interphase: before meiosis begins, genetic material is duplicated.First division of meiosis:

Proohase 1: duplicated chromatin condenses. Each chromosome consistsof two, closely associated sister chromatids. Crossing over can occur duringthe latter part of this stage.Metaphase 1: Homologous chromosomes align at the equatorial plate.Anaphase 1: Homologous pairs separate with sister chromatids remainingtogether.Telophase 1: two daughter cells are formed with each daughter containingonly one chromosome of the homologous pair.

Second division of meiosis:Prophase 2: DNA does not replicate.Metaphase 2: Chromosomes align at the equatorial plate.Anaphase 2: centromeres divide and sister chromatids migrate separately toeach pole. Telophase 2: cell division is complete.Four haploid daughter cells are obtained.Daughter cells have half the number of chromosomes found in the original parent cell and with crossing over, are genetically different.

Comparison Meiosis and Mitosis

2.- Mendelian Genetics

Gregor Mendel1822-1884

Austrian botanist monk. Considered to be the father of classical genetics.He spent many years studying pea plants(Pisum sativum) in the garden of themonastery. He wanted to find out how particular qualities are inherited whenplants are cross-fertilized.Barely acknowledged during his lifetime, Mendel’s work was rediscovered in 1900 and his laws were recognized.

Genetics TermsGenetics: this is the part of Biology which studies the transmissionof characteristics from one individual to its descendants.

Character or trait: this is each one of the characteristics whichare inherited from parents by offspring (colour of eyes, skin, etc.)

Gene: Each piece of DNA of the nucleus of a cell in which theinformation for a character is located.

Allele: they are the different forms of a gene.

Dominant allele: allele that is always expressed. A trait controlledby a dominant allele always shows up in the organism when theallele is present. It is symobolised with capital letters: A, B, C,etc.

Recessive allele: allele that is expressed only if dominant allele isnot present. A trait controlled by a recessive allele will only show up if the organism does not have the dominant allele. It issymobolised with lower case letters: a, b, c,etc.

Homozygotic: this is the individual which has two equal alleles fora specific character. It is symbolised with the same letters: AA, aa, BB, bb, etc.

Heterozygotic: this is the individual which has two different allelesfor a specific character. It is symbolised with one upper an onecase letter: Aa, Bb, Cc, bb, etc.

Genotype: this is the set of genes which a living being has in eachone of its cells.

Phenotype: this is the set of characteristics that are expressed ormanifested in a living being.

CrossThis symbolised the sexual union of a pair and the probable descendants:

Phenotypes X

black whiteBb bbGenotypes

B50%

b50%

b100%

Gametes

Bb bb

50% black 50% white

Genotypes

Phenotypes

Punnet SquareProbability diagram ilustrating thepossible offspring of a mating:

X

Yellow Green

Parental generation

aa

aGametes

F1 generation

AA

A

X

Aa

A

Aa

Aa aGametes50% 50% 50% 50%

aaAaa

AaAAA

aAGametesF2 generation

Punnet Square

75% 25%3 : 1

Mendel’s WorkMendel’s First Law (of uniformity):The first thing Mendel discovered was that if he crossed twodifferent but homozygotic individuals, their descendants wereuniform (all the same). By crossing a homozygotic plant withyellow seeds with another which was also homozygotic, but withgreen seeds, the resulting plants only produced yellow seeds. TheAA plant only produces A gametes and the aa plant only a gametes. The green colour of one of the parents did not appear in the descendants. This is known as dominance: the “colour ofseed” character is inherited by means of a pair of alleles, onedominant, which corresponds to “yellow” (A) and the otherrecessive, which corresponds to “green” (a); the parents werehomozygotic AA and aa (yellow and green), which means that theoffspring would be heterozygotic Aa and yellow, because thedominant allele does not allow the expression of the recessiveallele.

Mendel’s Second Law (independent segregation):When Mendel crossed the descendants obtained (F1) together, he found that the two kinds of seeds appeared in the secondgeneration (F2), three yellow and one green (3:1). The greenseeds appear again, which meant that F1, despite being yellow, carried information for the colour green. In fact the seeds of the F1generation were heterozygotic (Aa) and produced gametes of twokinds, A and a. The two hereditary factors that provideinformation on the same character did not fuse, and duringthe process of fertilization of the gametes, they segregated, or separated.

Smooth yellow Rough green

X

AABB aabb

P

AaBb

F1 X

AaBb

AB Ab aB ab25% 25% 25% 25%

G

aabbaaBbAabbAaBbab

aaBbaaBBAaBbAaBBaB

AabbAaBbAAbbAABbAb

AaBbAaBBAABbAABBAB

abaBAbABGametes F2

Smoothyellow

Roughyellow

Smoothgreen

Roughgreen

9 : 3 : 3 : 1

Mendel’s Third Law (independent combination):When studying the behaviour of two characters at the same time, such as colour (yellow and green) and the texture of the surface(smooth and rough), Mendel found that, if he began with smoothyellow homozygotic seeds (AABB) and rough green seeds (aabb), in the first generation he obtained uniform descendants whichwere smooth and yellow (AaBb) but in the second generation he obtained all the possible combinations of phenotypes in thefollowing proportions: 9:3:3:1. When he checked the characteresseparately, he saw that there were 12/16 yellow seeds as opposedto 4/16 green ones, and 12/16 smooth ones as opposed to 4/16 rough ones, which means 75% and 25% (3:1) as happened in accordance with the Law of independent segregation. Thus he deduced that when various characters combine together, heredity is independent and the proportions of phenotypes weredue to the dominance of the colour yellow and the smooth textureas opposed to the colour green and the rough texture.

CodominanceFor all of the traits that Mendel studied, one allele was dominantwhile the other was recessive. This is not always the case. Forsome alleles, an inheritance pattern called codominance exists. In codominance, the alleles are neither dominant nor recessive. As a result, both alleles are expressed in the offspring.

Look the picture. Mendel’s principle of dominant and recessivealleles does not expalin why the heterozygotic chickens have bothblack and white feathers. The alleles for feather color are codominant. As you can see, neither allele is masked in theheterozygotic chickens. Notice also that the codominant alleles are written as capital letters with superscripts (FB for black feathersand Fw for white feathers. As the Punnet square shows, heterozygotic chickens have the FB FW allele combination.

3.- Chromosomal Theory of Inheritance

ChromosomesWhen Mendel made his discoveries he didn’t know where the genetic informationwas to be found, nor what material it carried. Now we know that it is in the nucleus ofthe eucaryotic cells, more specifically in the deoxyribonucleic acid or DNA.

In the nucleus of the cell, the DNA molecules are practically invisible during theinterphase period due to their thickness. However, during mitosis, each one of theDNA molecules rolls itself up several times and combines with proteins in such a way that it becomes a structure known as a chromosome, and it is visible undermicroscope.

These are human chromosomes taken from a scanning electron microscope

Number of chromosomesThe number of chromosomes an organism has depends on its species. Allspecies have a characteristic number of chromosomes. The more complex anorganism is, the more chromosomes it will have. For example, humans are complex organisms and have 46 chromosomes when bacteria have only one.

Chromosomes can be counted and are visible only during the cell division(metaphase) because that is when the DNA is supercoiled and condensed tofacilitate distribution into daughter cells becoming into individual chromosomes. They can be coloured using specific techniques to differentiate one fromanother.

The parts of a chromosome are:Chromatid: one of the two identical parts of the chromosome after DNA replication.Centromere: the point where the two chromatids and microtubules attach.

In higher organisms each cell usually contains two similar copies of eachchromosome. One of this copies is a maternal contribution and the other is a paternal contribution. Together, these are called a homologous pair and eachalone is called a homologue.

The haploid number of a cell refers to the total number of homologous pairsin a cell (or number of unique chromosomes). In humans it is 23. The diploidnumber of a cell refers to the total number of chromosomes in a cell and isequal to two times the haploid number. In humans it is 46. If the haploid numberis thought of as n, the diploid number would be 2n.

Gametes are haploid (n) cells, because they have only one set ofchromosomes. Somatic cells are diploid (2n) cells because they have twosets of chromosomes, one from the mother, one from the father. When a maleand female gamete join (fertilization), a new diploid organism is formed (n + n = 2n).

The Karyotype is the representation of entire metaphase chromosomes in a cell, arranged in order of size.

centromere

chromatids

chromosome

Human Male Karyotype. The black and white banding pattern is due to a particular staining technique used to visualize and identify thechromosomes.

Genes on ChromosomesRemember that a gene is a segment of DNA. Each gene controls a trait. The allelesare different forms of a gene. Genes are located on chromosomes, which are made up of thousands of genes, there are about 35.000 in a single cell. Every cell in a bodycontains an identical set of 46 chromosomes, grouped in 23 pairs. Because genes are a part of chromosomes, they also come in pairs, and each gene pair workstogether to control a specific function or activity within cell. In other words, each oneof us has two copies of every gene. One set of copies is inherited from our mother, the other from our father. Each chromosome in a pair has the same genes but may have different alleles for some genes and the same alleles for others.

The molecular gene is a definite sequence of bases in the DNA chainwich together code for the production of a particular protein. A

difference in the sequence of bases between two copies of a gene wouldmean that these two copies are different alleles.

Notice that each chromosome in the pair has the same genes. Thisgenes are lined up in the same order on both chromosomes. However, the alleles for some of the genes might be different. For example, theorganism has the A allele on one chromosome and the a allele on theother. As you can see, this organism is heterozygotic for some traitsand homozygotic for others.

4.- MUTATIONSMutationsMutation is a change in the DNA of a cell, which is producedspontaneously and randomly. Mutations can cause a cell toproduce an incorrect protein during protein synthesis. As a result, the organism’s trait, or phenotype, may be different from what itnormally would have been.Mutations appear naturally, but their frequency can be significantlyincreased by the action of chemical products or radiations. Thesefactors are known as mutagenic agents.Types of mutations

Structural: some mutations are the result of small changes in anorganism’s hereditary material. For example, a single base may be substituted for another , or one or more bases may be removed froma section of DNA. This type of mutation can occur during the DNA replication process.

Numerical: they involve the loss or gain of one or more chromosomes. This type of mutation may occur when chromosomesdon’t separate correctly during meiosis. The cell could also end up with extra segments of chromosomes. When this type of mutationoccurs, the individual suffers a series of alterations and symptomswhich are known by the name of syndrome. The most well- knownare:Down’s syndrome or trisomy 21: an extra chromosome number 21.

Klinefelter: 44 + XXY

Turner: 44 + X0

Structuralmutations

Numericalmutations

Effects of MutationsBecause mutations can introduce changes in an organism, they can be a source of genetic variety.

A mutation is harmful to an organism if it reduces the organism’s chance for survival and reproduction. Whether a mutation is harmful or not depends pertly on theorganism’s environment. The mutation that led to the production of a white animal (albinism) would probably be harmful to an organism in the wild.The animal’s whitecolour would make it more visible, and thus easier for predators to find. However,,a white animal in a zoo has the same chance for survival as a brown animal. In a zoo, the mutation neither helps nor harms the animal.

Helpful mutations, on the other hand, improve an organism’s chances for survival and reproduction. Antobiotic resistance in bacteria is an example. Antibiotics are chemicals that kill bacteria. Gene mutations have enabled some kinds of bacteria to become resistant to certain antibiotics, that is, the antibiotics do not kill the bacteria that have the mutations. The mutations have improved the bacteria’s ability to survive and reproduce.

Albinism: lack of pigment in the skin, eyes as a result of a mutation.

Different morphological mutations in Fruit Flies (Drosophila melanogaster). This fly is a favorite “model” organism for genetics research.

5.- HUMAN INHERITANCEPatterns of Human Inheritance

Single genes with two alleles: a number of human traits are controlled by a single gene with one dominant allele and one recessive allele.These human traits have two distinctly differents phenotypes, or physical appearances. For example, a widow’s peak is a hairline that comes to a point in the middle of the forehead.

Single genes with multiple alleles: some human traits are controlled by a single gene that has more than two alleles. Such a gene is said to have multiple alleles, three or more forms of a gene that code for a single trait. Human blood type is controlled by a gene with multiple alleles. There are four main blood types: A, B, AB and O. Three alleles control the inheritance of blood types. The allele for blood type A and the allele for blood type B are codominant. The allele for blood type O is recessive. There are six possible genotypes which give rise to the four blood groups.

Traits controlled by many genes. Polygenic inheritance: some human traits show a large number of phenotypes because the traits are controlled by many genes. For example, at least four genes control heigh in humans, so there are many possible combinations of genes and alleles. Skin colour is another human trait that is controlled by many genes.

Widow’s peak Punnet SquareThis Punnet Square shows a cross between two parents with widow’s peaks who are heterozygotics for thistrait. The allele for a widow’s peak is dominant (W) over the allele for a straight hairline.

Many phenotypesSkin colour in humans is determined by three or more genes.

Blood group OAO

Blood group ABAB

Blood group BBO

Blood group BBB

Blood group AAO

Blood group AAA

PhenotypesGenotypes

Blood groups in humans

The sex chromosomesA human somatic cell contains two sets of homologous chromosomes, which may be divided into two types: there is a pair with different chromosomes, the sex chromosomes or heterochromosomes. The other chromosomes are the same and are called autosomes.The sex chromosomes carry genes that determine whether a person is male or female. They also carry genes that determine other traits.

Girl or Boy?The sex chromosomes are the only chromosome pair that do not always match. If you are girl, your two sex chromosomes match. The two chromosomes are called X chromosomes. If you are boy, your sex chromosomes do not match. One of them is an X chromosome, and the other is a Y chromosome. The Y chromosome is much smaller than the X chromosome.

Sex chromosomes and fertilizationSince both of a female’s sex chromosomes are X chromosomes, all eggs carry one X chromosome. Males, however, have two different sex chromosomes. Therefore, half of a male’s sperm cells carry an X chromosome, while half carry a Y chromosome. When a sperm cell with an X chromosome fertilizes an egg, the egg has two X chromosomes. The fertilizated egg will develop into a girl. When a sperm with a Y chromosome fertilizes an egg, the egg has one X chromosome and one Y chromosome. The fertilized egg will develop into a boy. This means that, depending on the sperm which intervenes inthe fertilization of the egg, the future individual will be male or female.

As this cross shows, there is a 50% probability that a child will be a girl and a 50% probability that a child will be a boy.

The Sex-Linked GenesThe genes for some human traits are carried on the sex chromosomes. Genes on the X and Y chromosomes are often called sex-linked genes because their alleles are passed from parent to child on a sex chromosome. Traits controlled by sex-linked genes are called sex-linked traits. One sex-linked trait is red-green colorblindness. A person with this trait cannot distinguish between red and green. Unlike most chromosome pairs, the X and Y chromosomes have different genes. Most of the genes on the X chromosome are not on the Y chromosome. Therefore, an allele on an X chromosome may have no corresponding allele on a Y chromosome.Like other genes, sex-linked genes can have dominant and recessive alleles. In females, a dominant allele on the other X chromosome will mask a recessive allele on the other X chromosome. But in males, there is usually no matching allele on the Y chromosome to mask the allele on the X chromosome. As a result, any allele on the X chromosome, even a recessive allele, will produce the trait in a male who inherits it. Because males have only one X chromosome, males are more likely than females to have a sex-linked trait that is controlled by a recessive allele.Hemophilia: It is agenetic disorder in which a person’s blood clots very slowly or not at all. People with this disorder do not produce one of the proteins needed for normal blood clotting. Hemophilia is also caused by a recessive allele on the X chromosome. Because it is a sex-linked disorder, it occurs more frequently in males than in females.

One important tool that genetics use to trace the inheritance of traits in humans is a pedigree. It is a chart or “family tree” that tracks which members of a family have a particular trait. The figure above shows the Queen Victoria-Family Tree tracing the inheritance of hemophilia in this family. Hemophilia played an important role in Europe’s history. It became known as the “Royal disease” bacause it spread to the royal families of Europa through Victoria’s descendants.