Lecture 3 PDF - Classical Genetics HU-BT III

CLASSICAL GENETICS HU-BT III Kazim Ali Assistant Professor Biotechnology  Course Outline Midterm Final 1. Classical Mendelian genetics (2- 1. Gene interactions; epistasis and multi...

CLASSICAL GENETICS HU-BT III Kazim Ali Assistant Professor Biotechnology  Course Outline Midterm Final 1. Classical Mendelian genetics (2- 1. Gene interactions; epistasis and multiple 5/9/24) 3 Classes alleles, ABO blood type alleles and Rh 2. Monohybrid crosses (9-12/9/24) factor alleles in humans 3 classes 2. Structure of chromosomes; Organization 3. Dihybrid and Trihybrid ratios of genes and genomes (16-26/9/24) 6 classes 3. Nucleic acid function 4. Principle of independent 4. DNA as warehouse of genetic assortment (30/9-3/10/24) 3 information classes 5. Experimental evidence that DNA is 5. Probability in Mendelian genetic material inheritance (7-17/10/24) 3 6. Sex determination; linkage and crossing classes over 6. Dominance, recessiveness, co- dominance, and incomplete- dominance 6 classes(21- 24/10/24)  Some Imporatnt Points 1. Mode of examination (MCQs based and online) 2. Midterm (October 28, 2024) 3. Assignment and Quiz (TBD) 4. Attendance Gregor Mendel, Father of Genetics Johann Gregor Mendel (1822–1884) was a lifelong learner, teacher, scientist, and man of faith. As a young adult, he joined the Augustinian Abbey in Brno (Czech Republic). Supported by the monastery, he taught physics, botany, and natural science courses at the secondary and university levels. In 1856, he began a decade-long research pursuit Gregor Mendel involving inheritance patterns in honeybees and plants, Gregor Mendel's work in pea led to ultimately settling on pea plants as his primary model our understanding system. In 1865, Mendel presented the results of his of the foundational experiments with nearly 30,000 pea plants to the local principles of Natural History Society. He demonstrated that traits are inheritance. transmitted from parents to offspring independently of other traits and in dominant and recessive patterns. In 1866, he published his work, Experiments in Plant Hybridization in the proceedings of the Natural History Society. Mendel’s studies of peas revealed the laws of inheritance Mendel’s studies of peas revealed the laws of inheritance...which help us understand human diseases such as sickle cell anemia... Mendel’s studies of peas revealed the laws of inheritance...and hemophilia, as well as countless other human diseases that have a genetic contribution. Pedigree of family carrying hemophilia allele Mendel’s studies of peas revealed the laws of inheritance Mendel’s work laid the foundation for the sciences of plant genetics and plant breeding. Distinguished plant breeder Norman Borlaug 1914-2009, Nobel Laureate 1970 Monoecious  Pea Plant Crossing Anthers Anthers Stigma Ovules Ovary Petals Peeled-back petal 1 In crossing peas, the anthers of the female parent are first exposed and then cut off to prevent self- Pea Plant Crossing fertilization. Anthers Anthers Stigma Ovules Ovary Petals Peeled-back petal  Pea Plant Crossing 2 3 Mature pollen is After fertilization, a small collected from another cloth bag is tied around the flower and deposited on fertilized flower to prevent the stigma of the female stray pollen from entering. parent. Flower on female parent Flower on male parent  Gregor Mendel's Hypotheses 1. Hereditary determinants are of a particulate nature. Each genetic trait is governed by unit factors, which "hang around" in pairs (or gene pairs) within individual organisms. 2. When two different unit factors governing the same phenotypical trait occur in the same organism, one of the factors is dominant over the other one, which is called the recessive trait. 3. During the formation of gametes the "paired" unit factors separate or segregate randomly so that each gamete receives either one or the other of the two traits, but only one.  Gregor Mendel's Hypotheses 4. The union of one gamete from each parent to form a resultant zygote is random with respect to that particular characteristic. 5. During production of gametes, only one of the "pair members" for a given character passes to the gamete. 6. When fertilization occurs, the zygote gets one from each parent, thus restoring the pair. Monohybrid Cross  X Monohybrid Cross Monohybrid Cross Monohybrid Cross Monohybrid Cross  YY Yy yy Homozygous Heterozygous Homozygous DOMINANT recessive  YY Yy yy Homozygous Heterozygous Homozygous DOMINANT recessive  YY Yy yy Homozygous Heterozygous Homozygous DOMINANT recessive  YY yy yy P1 generation y y y y 1/2 1/2 1/2 1/ 2 Y 1/2 Yy Yy Y 1/4 1/4 1/2 YY 1/4 Yy YY 1/ Y 4 Yy 1/2 Yy Yy 1/4 1/4 y 1/2 F1 generation yy yy 1/4 1/  YY yy P1 generation The Principle of Segregation Yy F1 generation Y y 1/2 1/2 Y Expected ratio of YY : Yy : yy 1/2 genotypes is 1 : 2 : 1 Yy Expected ratio of F1 generation y dominant:recessive 1/2 phenotypes is 3 : 1 F2 generation  Testcross Gametes from Gametes from homozygous homozygous recessive parent recessive parent yy yy y y y y 1/2 1/2 1/2 1/2 Gametes Gametes from Yy Y from YY Y individual 1/2 Yy Yy individual 1/2 Yy Yy 1/4 1/4 1/4 1/4 Yy YY y Y 1/2 yy yy 1/2 Yy Yy 1/4 1/4 1/4 1/4 ALL Heterozygous Heterozygous & genotypes Homozygous recessive genotypes 1:1. Mendel's 1st Law- The law of Segregation Mendel's 2nd Law- the Law of random/independent assortment  F1 Plant 1 F1 Plant 2 Dihybrid Cross  SSYY X ssyy YY SS yy ss SsYy F1 Plant 1 F1 Plant 2 Dihybrid Cross  YY SS yy ss F1 Plant 1 F1 Plant 2 Dihybrid Cross  Pollen gametes YS Ys yS ys 1/4 1/4 1/4 1/4 YS 1/4 YY SS YY Ss Yy SS Yy Ss 1/16 1/16 1/16 1/16 Independent Ovule gametes Ys 1/4 YY Ss YY ss Yy Ss Yy ss 1/16 1/16 1/16 1/16 Assortment yS 1/4 Yy SS Yy Ss yy SS yy Ss 1/16 1/16 1/16 1/16 ys 1/4 Yy Ss Yy ss yy Ss yy ss 1/16 1/16 1/16 1/16  Pollen gametes YS Ys yS ys 1/4 1/4 1/4 1/4 YS 1/4 YY SS YY Ss Yy SS Yy Ss 1/16 1/16 1/16 1/16 Independent Ovule gametes Ys 1/4 YY Ss YY ss Yy Ss Yy ss 1/16 1/16 1/16 1/16 Assortment yS 1/4 Yy SS Yy Ss yy SS yy Ss 1/16 1/16 1/16 1/16 ys 1/4 Yy Ss Yy ss yy Ss yy ss 1/16 1/16 1/16 1/16 Using Pedigrees to Study Inheritance Patterns Many human diseases are inherited genetically. A healthy person in a family in which some members suffer from a recessive genetic disorder may want to know if he or she has the disease- causing gene and what risk exists of passing the disorder on to his or her offspring. Of course, doing a test cross in humans is unethical and impractical. Instead, geneticists use pedigree analysis to study the inheritance pattern of human genetic diseases. Major Types of Genetic Disease Many, if not most, diseases have their roots in genes. Genes—through the proteins they encode—determine how efficiently foods and chemicals are metabolized, how effectively toxins are detoxified, and how vigorously infections are targeted. Genetic diseases can be categorized into three major groups: single-gene, chromosomal, and multifactorial. Thousands of diseases are known to be caused by changes in the DNA sequence of single genes. A gene can be changed (mutated) in many ways resulting in an altered protein product that is unable to perform its function. The most common gene mutation involves a change in a single base in the DNA—a misspelling. Other mutations include the loss (deletion) or gain (duplication or insertion) of a single or multiple bases. The altered protein product may still retain some function but at a reduced capacity. In other cases, the protein may be totally disabled by the mutation or gain an entirely new but damaging function. In addition, genetic diseases can be caused by larger changes in chromosomes. Chromosomal abnormalities may be either numerical or structural. The most common type of chromosomal abnormality is known as aneuploidy, an abnormal chromosome number due to an extra or missing chromosome. A normal karyotype (complete chromosome set) contains 46 chromosomes including an XX (female) or XY (male) sex chromosome pair. Structural chromosomal abnormalities include deletions, duplications, insertions, inversions, or translocations of a chromosome segment. Inheritance Patterns of Genetic Diseases The basic laws of inheritance are important in order to understand patterns of disease transmission Single-gene diseases are usually inherited in one of several patterns depending on the location of the gene (i.e., chromosomes 1-22 or X and Y) and whether one or two normal copies of the gene are needed for normal protein activity. There are five basic modes of inheritance for single- gene diseases: autosomal dominant, autosomal recessive, X linked dominant, X-linked recessive, and mitochondrial. Individuals carrying one mutated Affected individuals must carry copy of a gene in each cell will be two mutated copies of a gene affected by the disease. Only females can pass on Females are more Males are more frequently mitochondrial conditions to frequently affected than affected than females. their children (maternal males. Families with an X-linked inheritance Fathers cannot pass X- recessive disorder often linked traits to their have affected males, but sons (no male-to-male rarely affected females, in transmission). each generation.  People with the recessive genetic disease alkaptonuria cannot properly metabolize two amino acids, phenylalanine and tyrosine. Affected individuals may have darkened skin and brown urine, and may suffer joint damage and other complications. Pedigree of a human family with the recessive genetic disease alkaptonuria.  Dihybrid Cross In pea plants, purple flowers (P) are dominant to white flowers (p) and yellow peas (Y) are dominant to green peas (y). What are the possible genotypes and phenotypes for a cross between PpYY and ppYy pea plants? How many squares do you need to do a Punnett square analysis of this cross?  PpYY X ppYy PP/Pp pp PY pY pY py YY/Yy yy PpYY PpYy ppYY ppYy Purple Yellow Purple Green White Yellow White Green 2 0 2 0 Trihybrid Cross R/r S/s Y/y  Probability in Mendelian Genetics Forked-Line Method When more than two genes are being considered, the Punnett- square method becomes unwieldy. For instance, examining a cross involving four genes would require a 16 × 16 grid containing 256 boxes. It would be extremely cumbersome to manually enter each genotype. For more complex crosses, the forked-line and probability methods are preferred. To prepare a forked-line diagram for a cross between F1 heterozygotes resulting from a cross between AABBCC and aabbcc parents, we first create rows equal to the number of genes being considered, and then segregate the alleles in each row on forked lines according to the probabilities for individual monohybrid crosses.  Probability in Mendelian Genetics The forked-line method can be used to analyze a trihybrid cross. Here, the probability for color in the F2 generation (3 yellow:1 green), shape occupies the second row (3 round: 1 wrinkled), for height occupies the third row (3 tall:1 dwarf).  Probability in Mendelian Genetics Product rule Method To fully demonstrate the power of the probability method, however, we can consider specific genetic calculations. For instance, for a tetrahybrid cross between individuals that are heterozygotes for all four genes, and in which all four genes are sorting independently and in a dominant and recessive pattern, what proportion of the offspring will be expected to be homozygous recessive for all four alleles? Plant Height T/t Pod Shape R/r trsy? Seed Shape S/s Seed Color Y/y Rather than writing out every possible genotype, we can use the probability method. We know that for each gene, the fraction of homozygous recessive offspring will be 1/4. Therefore, multiplying this fraction for each of the four genes, (1/4) × (1/4) × (1/4) × (1/4), we determine that 1/256 of the offspring will be quadruply homozygous recessive. Principle of Independent Assortment Mendel’s principle of independent assortment states that genes do not influence each other with regard to the sorting of alleles into gametes, and every possible combination of alleles for every gene is equally likely to occur. Independent Assortment Independent assortment of genes in different chromosomes reflects the fact that non homologous chromosomes can orient in either of two ways that are equally likely. A A B b A B A b a b a B a b a B Anaphase I Anaphase I Resulting gametes Resulting gametes A A A A B B b b a a a a b b B B Independent Assortment Independent assortment of genes in different chromosomes reflects the fact that non homologous chromosomes can orient in either of two ways that are equally likely. A A B b A B A b a b a B a b a B Anaphase I Anaphase I Resulting gametes Resulting gametes A A A A B B b b a a a a b b B B Independent Assortment Independent assortment of genes in different chromosomes reflects the fact that non homologous chromosomes can orient in either of two ways that are equally likely. A A B b A B A b a b a B a b a B Anaphase I Anaphase I Resulting gametes Resulting gametes A A A A B B b b a a a a b b B B Independent Assortment Independent assortment of genes in different chromosomes reflects the fact that non homologous chromosomes can orient in either of two ways that are equally likely. A A B b A B A b a b a B a b a B Anaphase I Anaphase I Resulting gametes Resulting gametes A A A A B B b b a a a a b b B B Independent Assortment Independent assortment of genes in different chromosomes reflects the fact that non homologous chromosomes can orient in either of two ways that are equally likely. A A B b A B A b a b a B a b a B Anaphase I Anaphase I Resulting gametes Resulting gametes A A A A B B b b a a a a b b B B Independent Assortment Independent assortment of genes in different chromosomes reflects the fact that non homologous chromosomes can orient in either of two ways that are equally likely. A A B b A B A b a b a B a b a B Anaphase I Anaphase I Resulting gametes Resulting gametes A A A A B B b b a a a a b b B B chromosome 1 chromosome 7 chromosome 5 chromosome 4 chromosome 1 chromosome 4 chromosome 4 chromosome 1 chromosome 7 chromosome 5 chromosome 4 chromosome 1 chromosome 4 chromosome 4 chromosome 1 chromosome 7 chromosome 5 chromosome 4 chromosome 1 chromosome 4 chromosome 4  1/4 1/4 1/4 1/4 Full agreement with Mendel’s 2nd law Mendelian Genetics Extensions to Mendelian Genetics Incomplete dominance Codominance MuMulltitippllee AAleeleess Alternatives to Dominance and Recessiveness Since Mendel’s experiments with pea plants, other researchers have found that the principle of dominance does not always hold true. Instead, several different patterns of inheritance have been found to exist. Incomplete Dominance Mendel’s results, that traits are inherited as dominant and recessive pairs, contradicted the view at that time that offspring exhibited a blend of their parents’ traits. However, the heterozygote phenotype occasionally does appear to be intermediate between the two parents. For example, in the snapdragon, Antirrhinum majus, a cross between a homozygous parent with white flowers (CWCW) and a homozygous parent with red flowers (CRCR) will produce offspring with pink flowers (CRCW). Incomplete Dominance This pattern of inheritance is described as incomplete dominance, denoting the expression of two contrasting alleles such that the individual displays an intermediate phenotype. The allele for red flowers is incompletely dominant over the allele for white flowers. Incomplete dominance  X Incomplete Dominance CRCR CWCW P1 generation The phenotype of the heterozygous CRCW plant is CRCW intermediate, an example of incomplete F1 generation dominance. CR CW 1/ 1/ 2 2 CR 1/ 2 The result of segregation can be CRCR 1/ CRCW 1/ observed directly, because the ratio of 4 4 red:pink:white phenotypes is 1 : 2 : 1, CRCW which reflects the ratio of CW CRCR:CRCW:CWCW genotypes. 1/ 2 CRCW CWCW 1/ 1/ 4 4 F2 generation Mendelian Genetics Extensions to Mendelian Genetics Incomplete dominance Codominance Multiple Alleles  Codominance A variation on incomplete dominance is codominance, in which both alleles for the same characteristic are simultaneously expressed in the heterozygote.  Codominance Camelias & Cows https://rwu.pressbooks.pub/bio103/chapter/mendelian-genetics/ https://bccampusbiology.pressbooks.tru.ca/chapter/laws-of-inheritance/