Genetics: The Basic Principles of Heredity, Meiosis, and Mendel's Principles PDF

Genetics: the Basic Principles of Heredity, Meiosis and Mendel's Principles Class Foundation Year Course Fundamentals of Human Biology Code FUNBIO.20 Lecturer Learning outcomes At the end of this lecture, the learner will be able to ALO 1 Outline the process of meiosis in gameto...

Genetics: the Basic Principles of Heredity, Meiosis and Mendel's Principles Class Foundation Year Course Fundamentals of Human Biology Code FUNBIO.20 Lecturer Learning outcomes At the end of this lecture, the learner will be able to ALO 1 Outline the process of meiosis in gametogenesis ALO 2 Review the genetic terminology defining alleles, loci, dominant and recessive, phenotype, genotype, homozygous and heterozygous ALO 3 Discuss probability in relation to genetic experiments and the use of the Punnett square in testing experimental results. ALO 4 Explain Mendel’s Law of Segregation (mono-hybrid cross) and Independent Assortment (di-hybrid cross) 2  Genetics is the science of Heredity Similarities between parents and offspring Study of inheritance only begun from 1850s  ALO 1 Outline the process of meiosis in gametogenesis Greek word “meion”, = make smaller; type of cell division occurs at gametogenesis in animals and spore formation in plants; it involves 2 rounds of cell division and one division of the chromosomes; Meiosis halves of the number of C/somes; produces a haploid cell; (when the haploid gametes fuse to form the zygote at fertilization the full diploid number is restored) meiosis also involves an exchange of genetic material between holomogous chromosomes; thus the genetic information is redistributed in new combinations; meiosis in animals takes place in specialised reproductive structures, the testis and ovary; resulting in the production of sperm and ova; Gamete production involves more than just meiosis and this will be discussed later.¶ Meiosis http://vle.rcsi.ie/file.php/1947/ Genetics_Videos/19.1-meiosi s.mov 1) Chromatids become replicate chromosomes; 2) Maternal and paternal Homologues associate together; 3) Form Tetraploid, C/some cross-over; 4) Chromosome synapsis at chiasmata; 5) Align at metaphase plate, separate; 6) A second alignment and separation occurs; 7) Produce 4 uniquely different cells  CENTRIOLES CENTROMERE Pre-meiotic Interphase is the same as in mitosis with a longer S-phase; DNA & organelles duplicate, ATP is stored for meiosis NUCLEAR NUCLEOLUS ENVELOPE Meiosis – Prophase 1 1. Leptotene 2. Zygotene 3. Pachytene 4. Diplotene 5. Diakinesis During prophase the homologous chromosomes are held together by a ‘synaptonemal complex’ of proteins which promote crossing over of sections of DNA between non-sister chromatids  Meiosis – Prophase 1 This is usually divided into five substages: 90% meisosis 1. Leptotene - the chromosomes become visible in the nucleus for the first time; 2. Zygotene - homologous chromosomes begin to pair or synapse along their length; 3. Pachytene - the pairing is complete, the chromosomes becoming coiled around one another forming a bivalent; Meiosis – Prophase 1 4. Diplotene each chromosome is now visibly divided into two closely paired chromatids; the attraction between the chromosomes now replaced by repulsion - the figure is now called a tetrad; chiasmata are formed - where two non-sister chromatids have broken in corresponding positions and rejoined in new combinations; About 40 recombinations per gamete in humans; the coiling of the homologous chromosomes is partially undone; ¶ Meiosis – Prophase 1 5. Diakinesis chromatids contract maximally but the pairs of chromosomes remain held by the attraction between the sister chromatids beyond the points of crossing-over; meanwhile the centrioles have separated and moved to opposite poles of the cell; nucleoli disappear and the nuclear envelope breaks down;  Chiasma Tetrad formation formation Recombination Crossing over at Chiasmata Gives genetic variation Is normal because they are homologues Clinical note: since Chromosomes are tightly packed, sometimes they can break e.g. during crossing over This can cause genetic syndromes if the cell becomes fertilized.  Meiosis I Metaphase I Anaphase I - Telophase I - the attraction between The tetrads become the homologous a short Telophase occurs orientated on the chromosomes lapses; at the end of the First metaphase plate; chromosomes separate Meiotic Division; the chromosomes of and are pulled to the in some species nuclear poles of the cell; each tetrad are on the centromeres do envelopes reform, opposite sides of the chromatids slightly NOT divide at this stage; equator; decondense followed by cytokinesis but there is no Interphase;  2nd Meiotic Division Metaphase II - Anaphase II - Since the chromatids do not properly centromeres now divide and the decondense there is no Prophase in the sister chromatids, now chromosomes, are pulled to the Second Meiotic Division; opposite poles of the cell;¶ the centrioles divide again and form two spindles at right angles to the plane of First Division; the haploid chromosomes orientate on the metaphase plate;  Meiosis - Telophase II Four nuclei are formed each with half the number of chromosomes in the original cell; new nuclear envelopes reform and nucleoli are reconstituted; chromosomes desporalise to become chromatin fibres again; cytokinesis now follows with cell membranes forming in the regions of the equatorial plates;  ALO 1 Outline the process of meiosis in gametogenesis Stages of meiosis. (a) Pre-meiotic interphase. (b) Leptotene. (c) Zygotene. (d) Pachytene. (e) Diplotene/ diakinesis. (f) Metaphase I. (g) Anaphase I/Telophase. (h) Metaphase II. (i) Anaphase II. (j) Telophase II. Read more about meiosis: http://www.answers.com/topic/meiosis#ixzz26GUzoIIH ALO 2 Review the genetic terminology defining alleles, loci, dominant and recessive, phenotype, genotype, homozygous and heterozygous Alleles and loci: the region on the chromosome occupied by the alleles of a particular gene is the Locus/loci the normal gene is called the Wild Type allele; should the other gene be dissimilar or abnormal it is called the Mutant allele Dominant and recessive: are, by convention, written in UPPER and lower case letters respectively; [“T” tallness ; “t” shortness] Phenotype - is (physical) appearance of the individual due to gene expression; Blonde hair or blue eyes Genotype - is the genetic constitution of the individual in symbolic form i.e. TT, Tt, tt Homozygous - two identical alleles at a particular pair of loci; e.g. TT Heterozygous - two different alleles at a particular pair of loci; e.g. Tt Germ cell – a gamete or a cell giving rise to a gamete; Somatic cell - all other cells in the body.  Each diploid cell has two sets of chromosomes, the 2n number. A gamete has one Members of one set can be paired set of with members of the other set. The chromosomes, the n members of a given pair correspond number. in shape, size, and type of genetic It carries one information, and are referred to as chromosome of homologous chromosomes. For each homologous pair. A given purposes of illustration each gamete can only chromosome is shown in the possess one unduplicated state. gene of any Gene Ioci particular pair of alleles. These chromosomes are nonhomologous. Each chromosome Is made up of perhaps thousands of Genes. The genes occupy definite Physical locations on the Chromosomes known as gene loci. When the gametes fuse, the resulting zygote has homologous pairs of A pair of chromosomes. There alleles These chromosomes are are homologous. Because diploid shown physically organisms possess pairs of paired for homologous chromosomes, the purposes of genes borne at corresponding loci of illustration. One the pair also occur in pairs. Genes member of each pair that occupy the same locus on each is of of a pair of chromosomes are said to maternal origin (red) and the be alleles. Allelic genes govern the other is paternal same kind of characteristics of the (blue). Each organism. pair bears allelic These genes genes. are not allelic to one another Alleles controlling fur color: Black Brown Although alleles govern the same kinds of characteristics., they do not necessarily contain identical information. Long Short Alleles controlling fur length: ALO 3 Discuss probability in relation to genetic experiments. " In a large random-mating population, gene and genotype frequencies remain constant in the absence of migration, mutation and selection. ” R. J. Berry. 1982 Suppose a pair of alleles (A) and (a) occur in a population at a frequency of (A) = 50% and (a) = 50%; to get the frequency of the genotypes we multiply the frequency of the alleles in the sperms and eggs in the population; so (0.5A + 0.5a) sperms x (0.5A + 0.5a) eggs or to use Punnett’s square:¶  Probability in genetics and the Punnet square Genotype Aa x Aa – AA- Homozygous dominant (p2) Punnet square: – aa- Homozygous recessive (q2) Crossing gametes of parents – Aa or aA –heterozygous (pq.pq) the variations and probabilities can be calculated. …(2pq) – p+q=1 (Total population 100%) The result = 0.25AA + 0.5Aa + 0.25aa; Gametes 0.5A 0.5a If we substitute the letters (p) and (q) for (A) and (a) we transform; 0.25 0.25 0.5A = 0.25pp + 0.5pq + 0.25qq, AA Aa 0.25 0.25 Since p + q = 1 (population 0.5a equation) aA aa Square both sides of the equation 0.25AA + 0.5Aa + 0.25aa (Hardy  (p+q) = (1 ) = 1 2 2 - Weinberg equation) p2 + 2pq + q2 = 1 Example 1: Calculate the number of carriers for Tay-Sachs disease in a Jewish European city of 20,000 with 2 newborn with the disease 2/20,000= 0.0001 have the disease (aa) (q2) q= 0.001, p+q=1 then p=0.99 p2 + 2pq + q2 =1 So, 2pq= 0.02 0.02*20,000= 400 So 1/50 people are carriers Tay-Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. It is most notable at 3-6months where a baby loses the ability to crawl.  Genotypic frequencies  E.g.2 This formula can be used to calculate the genotype frequencies from the allele frequencies (on the assumption of random mating); gametes 0.7p 0.3q  suppose the pair of alleles are in the ratio 70% (A) and 30% (a); 0.49 0.21  substituting (p) and (q) for (A) & (a); 0.7p pp pq   (0.7p + 0.3q) x (0.7p + 0.3q)¶ 0.21 0.09 0.3q In the F1 generation qp qq 0.49p2 + 0.42pq + 0.09q2 = p2 + 2pq + q2; the genotype frequencies are 49%(AA), 42%(Aa) and 9% (aa); The Hardy-Weinberg Principle states that these proportions ie. 70% (A) and 30% (a) will remain stable in the next and succeeding generations; to prove this we must calculate the allele frequencies from the genotypes; 0.49p2 + 0.42pq + 0.09q2 = p2 + 2pq + q2; The frequency of allele (A) = genotype AA + 1/2 Aa; i.e. All the homozygous dominant alleles plus half the heterozygous alleles 0.49 + 1/2(0.42) = 0.49 + 0.21 = 0.7; The frequency of the allele (a) = genotype aa + 1/2 Aa; i.e. all the homozygous recessive alleles plus half the heterozygous alleles 0.09 + 1/2 (0.42) = 0.09 + 0.21 = 0.3; So (A) = 0.7 and (a) = 0.3 or gene frequencies are 70% (A), 30% (a) in the subsequent generation; ALO 4 Explain Mendel’s Law of Segregation (mono-hybrid cross) and Independent Assortment (di- hybrid cross) How is biological information transferred from one generation to another?  Gregor Mendel; (1822 –1884) scientist and Augustinian friar interested in plant breeding. 1856 - 1863 he conducted experiments on hybridization of pure lines of garden peas; from these he deduced the Principles of Inheritance; (We will discuss Mendels first law of segregation and second law of independent assortment) 1866 he published a paper on his work in the "Proceedings of the Brünn Society for the Study of Natural History";  the paper was ignored or misunderstood for next 34 years; Until 1900 the paper was rediscovered on independently reviewing the literature by three botanists: Hugo de Vries in Holland; Karl Correns in Germany; Eric von Tschermak in Austria;  but it was not until the beginning of the 20th century that genetics as a science really began; ALO 4 Explain Mendel’s Law of Segregation (mono-hybrid cross) and Independent Assortment (di-hybrid cross) -Using pure breeding lines he crossed alternate ‘factors’ e.g. tall pea crossed with short pea plant -direct cross breeding (pollen of male to stigma of female) -scientific control by removing anthers and covering flowers with muslin bags TT- Tall phenotype; Tt – Tall phenotype; tt – short phenotype -The first generation offspring were called the first filial generation F1 generation The following year he crossed these offspring (self-cross/ self-pollinate) This produced a second filial F2 generation The F2 generation included 787 tall and 277 short plants, a ratio of about 3:1. Thus, Mendelian traits pass to successive generations in fixed ratios. ALO 4 Explain Mendel’s Law of Segregation (mono-hybrid cross) and Independent Assortment (di- hybrid cross) MENDEL'S FIRST LAW - LAW OF SEGREGATION "Characters are controlled by pairs of genes the members of which separate, or segregate, from one another during the formation of the germ cells and pass into different gametes. The pairs are restored at fertilization which allows their recombination in definite proportions. Consequently the characters to which they give rise may also segregate; for they appear in subsequent generations with definite numerical frequencies. ” E. B. Ford (1942);  First Law - F1 Generation All the resulting offspring termed the F1 or first filial generation will be heterozygotes (Bb) Bb = black in colour; We represent the matings using a Punnett square.¶ The parents are termed the P1 or first parental: Punett square F1 Generation all are Bb P1 gametes b b B Bb Bb B Bb Bb Well if we self cross the F1 generation (heterozygote Bb)….. So what next…? we get the first of our Mendelian frequencies;  First Law - F2 Generation as the gametes of the F1 will have either a (B) F1 or a (b) allele; gametes B b we expect a random combination of the two types leading to a definite mathematical ratio; B BB Bb There are 4 combinations all equally probable in the F2 (second filial) generation:¶ b bB bb As (Bb) and (bB) are similar the genotypic ratio is 1 : 2 : 1; but since the (B) allele is dominant the phenotypic ratio 3 : 1 three black mice to one brown mouse;  Law of Segregation ?? Suppose we wished to find which of these black mice are homozygous or heterozygotes?; we cross a black mouse from F2 generation with the if the black mouse is a heterozygote the offspring will be parental homozygous recessive brown mouse (bb); black heterozygous or homozygous brown recessive in a 1 : 1 ratio; If the black mouse is homozygous all the offspring will this is called a BACKCROSS (also called a test cross) be black and was first used by Mendel; it is important in testing genotypes in genetic experiments. gametes B B gametes B b b Bb Bb b Bb bb b Bb Bb b Bb bb Table 11-1 p231  MENDEL'S SECOND LAW - LAW OF INDEPENDENT ASSORTMENT "When two or more pairs of genes segregate simultaneously, the distribution of any one of them is independent of the distribution of the others. ” E. B. Ford 1942 If we consider two characters segregating in a 3 : 1 ratio; assuming nothing interferes with the random distribution of each; the two ratios will produce 16 possible combinations of the two characters or a 9 : 3 : 3 : 1 ratio in the F 2 generation; using the mouse model of black dominant homozygous (BB) and brown coloured recessive (bb); and allele for short hair (S) dominant to the long haired allele (s);¶  MENDEL'S SECOND LAW - LAW OF INDEPENDENT ASSORTMENT P1 If we mate the double homozygotes for the characters gametes BS BS black short hair (BBSS) and brown long hair (bbss); P1 gametes BS; BS X bs; bs bs BbSs BbSs we produce the heterozygous F1 generation (BbSs); bs BbSs BbSs F1 BS Bs bS bs these F1 mice produce four different gametes types of gametes; (BS), (Bs), (bS) and BS BBSS BBSs BbSS BbSs (bs); random mating of the F1 generation will Bs BBSs BBss BbSs Bbss result in 16 possible combinations in the F2 generation, a 9 : 3 : 3 : 1 ratio:¶ bS BbSS BbSs bbSS bbSs bs BbSs Bbss bbSs bbss  Law of Independent Assortment Backcross (testcross) This is used to determine the true double heterozygote (BbSs); BbSs can produce 4 haploid gametes – BS, Bs, bS, bs. Once more the P1 double homozygous recessive is used (bbss); We get four types of genotypically and phenotypically different offspring in a 1 : 1 : 1 : 1 ratio gametes BS Bs bS bs bs BbSs Bbss bbSs bbss Mendel’s Second Law does not apply if the two pairs of genes are situated on the same pair of chromosomes. In this case the genes are linked together Thank you F O R M O R E I N F O R M AT I O N P L E A S E C O N TA N T NAME SURNAME EMAIL: [email protected]