Week 10 PPT Mendelian Genetics PDF

Mendelian Genetics Raihana M. Abdulhamid, RMT Learning Objectives At the end of the lecture, the students should be able to: 1. Narrate Gregor Mendel’s experiment on pea plants as basis of transmission genetics 2. Differentiate the mechanisms of X-linked, Sex-limited and Sex-influenced...

Mendelian Genetics Raihana M. Abdulhamid, RMT Learning Objectives At the end of the lecture, the students should be able to: 1. Narrate Gregor Mendel’s experiment on pea plants as basis of transmission genetics 2. Differentiate the mechanisms of X-linked, Sex-limited and Sex-influenced inheritance. 3. Generate possible genetic outcomes by following the laws of inheritance. 4. Make a pedigree analysis of a given genetic situation. Introduction to Mendelian Genetics Who is the “Father of Genetics”?  Gregor Johann Mendel ❏ Often called the “father of genetics”. ❏ Became a priest at an atypical Augustinian monastery where the priests were teachers and did research in natural science. ❏ Here, Mendel learned how to artificially pollinate crop plants to control their breed.  Gregor Johann Mendel ❏ From 1857 to 1863, Mendel crossed and cataloged traits in 24,034 plants, through several generations. ❏ He deduced that consistent ratios of traits in the offspring indicated that the plants transmitted distinct units. ❏ He derived two hypotheses to explain how inherited traits are transmitted. Mendel’s Experiment Peas are ideal for heredity because they are easy to grow, develop quickly, and have many traits that take one of two easily distinguishable forms. When analyzing genetic crosses, the FIRST GENERATION is the parental generation, or P 1 ; the SECOND GENERATION is the first filial generation, or F 1 ; the NEXT GENERATION is the second filial generation, or F 2 , and so on. Mendel’s Experiments Gregor Mendel studied the transmission of seven traits in the pea plant. Each trait has two easily distinguished expressions, or phenotypes. Mendel’s Experiments ★ Mendel’s first experiments dealt with single traits with two expressions, such as “short” and “tall”. ★ He set up all combinations of possible artificial pollinations, manipulating fertilizations to cross tall with tall, short with short, and tall with short plants. ★ This last combination, plants with one trait variant crossed to plants with the alternate, produces hybrids, which are offspring that inherit a different gene variant from each parent. Mendel’s Experiments ★ Short plants crossed to other short plants were “true-breeding,” always producing short plants. ★ Some tall plants were true-breeding, but others crossed with each other yielded short plants in about one-quarter (¼) of the next generation. ★ It appeared as if in some tall plants, “tallness could mask shortness”. ○ One trait that masks another is said to be DOMINANT. ○ The masked trait is RECESSIVE. The other term for the Second Generation. A trait that masks another. Mendel’s Monohybrid Cross The Law Of Segregation. Monohybrid Cross Mendel conducted up to 70 hybrid crosses for each of the seven traits. Because one trait is followed and the parents are hybrids, this is called a monohybrid cross. Monohybrid Cross I. When Mendel crossed true-breeding tall plants with short plants, the next generation plants were all tall. II. When he self-crossed the F1 plants, one-quarter of the plants in the next generation, the F2 , were short, and three-quarters were tall. III. Of the tall plants in the F2 , one-third were true-breeding, and the other two-thirds were not true-breeding. THE LAW OF SEGREGATION In these experiments, Mendel confirmed that hybrids hide one expression of a trait—short, in this case—which reappears when hybrids are self-crossed. This is called the law of segregation. THE LAW OF SEGREGATION - reflects the actions of chromosomes and genes during meiosis. Because a gene is a long sequence of DNA, it can vary in many ways. ★ An individual with two identical alleles for a gene is homozygous for that gene. ★ An individual with two different alleles is heterozygous —what Mendel called “non-true-breeding” or “hybrid.” THE LAW OF SEGREGATION When considering a gene with two alleles: the dominant one is shown as a CAPITAL LETTER (ex. Tall = T) the recessive with the corresponding small letter (ex. Short = t). If both alleles are recessive, the individual is HOMOZYGOUS RECESSIVE. —> two small letters (ex. Tt = short). An individual with two dominant alleles is HOMOZYGOUS DOMINANT. —> two capital letters ( ex. TT = tall). One dominant and one recessive allele, such as Tt for non-true-breeding tall pea plants, indicates HETEROZYGOTES. —> one capital and small letter (ex.Tt = tall) THE LAW OF SEGREGATION An organism’s appearance does not always reveal its alleles. Both a TT and a Tt pea plant are tall, but TT is a homozygote and Tt a heterozygote. ★ The GENOTYPE describes the organism’s alleles, ★ The PHENOTYPE describes the outward expression of an allele combination. ○ A wild type phenotype is the most common expression of a particular allele combination in a population. The wild type allele may be recessive or dominant. ○ A mutant phenotype is a variant of a gene’s expression that arises when the gene undergoes a change, or mutation. Mendel’s first law—Gene Segregation. An individual with two identical alleles for a gene. Other term for heterozygous. Monohybrid Cross When Mendel crossed short plants ( tt ) with true-breeding tall plants ( TT ), ➔ tt X TT ➔ the seeds grew into F 1 plants that were all tall (Tt ). Monohybrid Cross Next, he self-crossed the F 1 plants. The progeny were TT, tt, and Tt. Genotypic ratio = 1 TT: 2 Tt: 1 tt. Phenotypic ratio = 3 tall plants to 1 short plant, a 3:1 ratio. Mendel saw these results for all seven traits that he studied. A diagram called a Punnett square shows these ratios. Punnett square - illustrates how alleles combine in offspring. - The different types of gametes of one parent are listed along the top of the square, with those of the other parent listed on the left side. - Each compartment displays the genotype that results when gametes that correspond to that compartment join. Test cross. Breeding a tall pea plant with homozygous recessive short plants reveals whether the tall plant is true-breeding (TT) or non-true-breeding (Tt). *Punnett squares usually indicate only the alleles. Mendel’s Law of Segregation A diagram that illustrates how alleles combine in offspring. Crossing an individual of unknown genotype with a homozygous recessive individual. Mendel’s Dihybrid Cross The Law Of Independent Assortment. Mendel’s Second Law ➔ The second law, the law of independent assortment, states that for two genes on different chromosomes, the inheritance of one does not influence the chance of inheriting the other. Two genes that are far apart on the same chromosome also appear to independently assort, because so many crossovers occur between them that it is as if they are carried on separate chromosomes Mendel’s second law — Independent Assortment. The independent assortment of genes carried on different chromosomes results from the random alignment of chromosome pairs during metaphase of meiosis I. Dihybrid Cross Mendel looked at seed shape, round or wrinkled (determined by the R gene), and seed color, yellow or green (determined by the Y gene). When he crossed true-breeding plants that had round, yellow seeds to true-breeding plants that had wrinkled, green seeds, all the progeny had round, yellow seeds. These offspring were double heterozygotes, or dihybrids, of genotype RrYy. *From their appearance, Mendel concluded that round is dominant to wrinkled, and yellow to green. Dihybrid Cross He self-crossed the dihybrid plants in a dihybrid cross (two genes and traits are followed). Mendel found four types of seeds in the next, third generation: 1. 315 plants with round, yellow seeds; 2. 108 plants with round, green seeds; 3. 101 plants with wrinkled, yellow seeds; 4. 32 plants with wrinkled, green seeds. These classes occurred in a ratio of 9:3:3:1. Dihybrid Cross Mendel then took each plant from the third generation and crossed it to plants with wrinkled, green seeds (genotype rryy ). Each parent would produce equal numbers of four different types of gametes: RY, Ry, rY, and ry. *Note that each of these combinations has one gene for each trait. Dihybrid Cross A Punnett square for this cross shows that the four types of seeds: 1. Round, yellow ( RRYY, RrYY, RRYy, and RrYy ) 2. Round, green ( RRyy and Rryy ) 3. Wrinkled, yellow ( rrYY and rrYy ) and 4. Wrinkled, green (rr yy ) Phenotypic Ratio = 9:3:3:1 The Product Rule ➔ An application of probability theory, can predict the chance that parents with known genotypes can produce offspring of a particular genotype. ➔ It states that the chance that two independent events will both occur equals the product of the chance that either event will occur alone. The product rule Consider the probability of obtaining a plant with wrinkled, green peas (genotype rryy ) from dihybrid ( RrYy ) parents Law of Independent Assortment Until recently, Mendel’s second law has not been as useful in medical genetics as the first law, because not enough genes were identified to follow the transmission of two or more traits at a time. It is common now to screen for hundreds or thousands of alleles or expressed genes at once. Computer analysis of many gene combinations has largely replaced Punnett squares.  “For two genes on different chromosomes, the inheritance of one does not influence the chance of inheriting the other”. Mendel’s Trihybrid Cross Trihybrid Cross ➔ A trihybrid cross is between two individuals that are heterozygous for three different traits. ➔ We will build on previous examples and again examine pea shape and pea color and then a new trait: pod shape. Our trihybrid cross example: RrYyCc x RrYyCc Trihybrid Cross Trihybrid Cross The gametes for each parent in a trihybrid cross would be RYC, RYc, RyC, Ryc, rYC, rYc, ryC, ryc, with one-eighth of a chance for any of them. Trihybrid Cross Phenotypic ratio= 27:9:9:9:3:3:3:1 ❖ 27= round, green, smooth pod ❖ 9= round, green, constricted pod ❖ 9= round, yellow, smooth pod ❖ 3= round, yellow, constricted pod ❖ 9= wrinkled, green, smooth pod ❖ 3= wrinkled, green, constricted pod ❖ 3= wrinkled, yellow, smooth pod ❖ 1= wrinkled, yellow, constricted pod Genotypic ratio: 1: RRYYCC 2: RrYYCC 1: rrYYCC 2: RRYYCc 4: RrYYCc 2: rrYYCc 1: RRYYcc 2: RrYYcc 1: rrYYcc 2: RRYyCC 4: RrYyCC 2: rrYyCC 4: RRYyCc 8: RrYyCc 4: rrYyCc 2: RRYycc 4: RrYycc 2: rrYycc 1: RRyyCC 2: RryyCC 1: rryyCC 2: RRyyCc 4: RryyCc 2: rryyCc 1: RRyycc 2: Rryycc 1: rryycc Gene Expression When Gene Expression Appears to Alter Mendelian Ratios In other cases, transmission patterns of a visible trait are not consistent with autosomal recessive or autosomal dominant inheritance. In these instances, either the nature of the phenotype or influences from other genes or the environment alter phenotypic ratios. Lethal Allele A genotype (allele combination) that causes death is lethal. Tay-Sachs disease is lethal by age 3 or 4 Huntington disease may not be lethal until late middle age Lethal genotype — causes death before the individual can reproduce, which prevents passage of genes to the next generation. Multiple Alleles An individual has two alleles for any autosomal gene—one allele on each homolog. However, a gene can exist in more than two allelic forms in a population because it can mutate in many ways Incomplete or Partial Dominance and Codominance Different Dominance Relationships Complete dominance - one allele is expressed, while the other isn’t. Incomplete dominance - the heterozygous phenotype is intermediate between that of either homozygote. Incomplete Dominance F1 hybrids have an appearance somewhat in between the phenotypes of the two parental varieties. Ex: snapdragons (flower) Red flower (RR) X White flower (rr) r r Produces the F1 generation R Rr Rr All Rr = Pink flower (heterozygous pink) R Rr Rr  Incomplete dominance Familial hypercholesterolemia (FH) is an example of incomplete dominance in humans. A heterozygote for familial hypercholesterolemia (FH) has approximately half the normal number of cell surface receptors in the liver for LDL cholesterol. An individual with two mutant alleles has the severe form of FH, with liver cells that totally lack the receptors. As a result, serum cholesterol level is very high. Codominance ➔ Different alleles that are both expressed in a heterozygote. ➔ The ABO blood group is based on the expression of codominant alleles. ◆ People in blood group AB have both antigen types. ◆ Type O red blood cells lack both A and B antigens. ➔ The A and B alleles are codominant, and both are completely dominant to O. Codominance ABO blood types are based on antigens on red blood cell surfaces. This depiction greatly exaggerates the size of the A and B antigens. Genotypes are in parentheses. The older I system, ABO blood types have been described as variants of a gene called “ I ”. (“ I ” stands for isoagglutinin) Codominance The I^A and I^B alleles of the I gene are codominant, but they follow Mendel’s law of segregation. These Punnett squares follow the genotypes that could result when a person with type A blood has children with a person with type B blood. Factors That Alter Single-Gene Phenotypic Ratios Factors That Alter Single-Gene Phenotypic Ratios  A heterozygous phenotype is intermediate between that of either homozygote. Sex-linked, Sex-limited or Sex-influenced Inheritance Sex Inheritance Sex Inheritance Sex-Linked Sex-Limited Traits Sex-Influenced Traits Traits Sex Inheritance Sex Inheritance Sex-Linked Sex-Limited Traits Sex-Influenced Traits Traits Allosome Autosome Sex Linked Traits ➔ Sex linked inheritance is a trait carried in either the X or the Y chromosome. ➔ A trait that is due to genes present on the X chromosome is more likely to be expressed in males as they have only one X chromosome. ➔ The presence of two X chromosomes in females can suppress its expression when one of them has the genes for the trait and the other does not. Sex Linked Traits ➔ Genes on either the X or the Y have unusual inheritance patterns and are called sex-linked. ➔ X-linkage is much more common than Y-linkage (since there are many more genes on the X than the Y). ➔ Since a female has two X chromosomes, she will have two copies of each X-linked gene. ◆ X linked traits fall under many categories like recessive, dominant and codominant which influence their expression in members of both the sexes. ◆ A trait due to a gene in the Y chromosome will only show in males and not in females. Examples of Sex Linked traits ❏ Red Green Colour blindness ❏ Hemophilia ❏ Duchenne Muscular Dystrophy ❏ Hairy Ears (Y chromosome)  Sex Limited Traits ➔ Sex-limited genes are genes which are present in both. ➔ These are genes that occur in both sexes (probably on the autosomes) but are normally expressed only in the gender having the appropriate hormonal determiner (activator). ➔ Throughout the pedigree the trait appears in only one sex, but it need NOT occur in all member of that sex. ➔ The genes for the trait can be carried and transmitted by the opposite sex although it is NOT displayed in that sex because of anatomical or physiological differences. Examples of Sex Limited traits ❏ The genes that control milk yield and quality in dairy cattle, for example, are present in both bulls and cows, but their effects are expressed only in the female cattle. ❏ Beard in males ❏ Barred coloring in chickens normally is visible only in the roosters. ❏ Secondary hormonal development Sex Influenced Traits ➔ Sex-controlled trait, also called Sex-influenced trait, a genetically controlled feature that may appear in organisms of both sexes but is expressed to a different degree in each. ➔ Sex-influenced traits are autosomal traits that are influenced by sex. ➔ The character seems to act as a dominant in one sex and a recessive in the other. Examples of Sex Influenced traits ❏ Male Pattern Baldness ❏ Length of index finger ❏ Body hair ❏ Muscle mass Types of traits in Sex Inheritance Pedigree Analysis Pedigree Charts called pedigrees display family relationships and depict which relatives have specific phenotypes and, sometimes, genotypes. ★ A pedigree in genetics differs from a family tree in genealogy, and from a genogram in social work, in that it indicates disorders or traits as well as relationships and ancestry. Pedigree components ❖ Symbols representing individuals are connected to form pedigree charts, which display the inheritance patterns of particular traits. Pedigree components Pedigrees Then and Now ❏ The earliest pedigrees were strictly genealogical, not indicating traits. ❏ The term pedigree arose in the fifteenth century, from the French pie de grue, which means “crane’s foot.” ❏ Pedigrees at that time, typically depicting large families, showed parents linked by curved lines to their many offspring. The overall diagram often resembled a bird’s foot. Pedigrees Then and Now ❏ One of the first pedigrees to trace an inherited illness was an extensive family tree of several European royal families, indicating which members had the clotting disorder hemophilia. ❏ The mutant gene probably originated in Queen Victoria of England in the nineteenth century. Pedigrees Then and Now ❏ In 1845, a genealogist named Pliny Earle constructed a pedigree of a family with colorblindness using musical notation— half notes for unaffected females, quarter notes for colorblind females, filled-in and squared-off notes to represent the many colorblind male. ❏ Today, pedigrees are important both for helping families identify the risk of transmitting an inherited illness and as starting points for identifying a gene from the human genome sequence. Pedigrees Display Mendel’s Laws ➔ Consider a pedigree for an autosomal recessive trait, albinism. ➔ Homozygous recessive individuals in the third (F2 ) generation lack an enzyme necessary to manufacture the pigment melanin and, as a result, hair and skin are very pale. ➔ Their parents are inferred to be heterozygotes (carriers). One partner from each pair of grandparents must also be a carrier. Pedigrees Display Mendel’s Laws ➔ An autosomal dominant trait does not skip generations and can affect both sexes. ➔ A typical pedigree for an autosomal dominant trait has some squares and circles filled in to indicate affected individuals in each generation. Huntington disease reverberates through a family, striking each generation until all affected individuals do not have children who have inherited the mutation. What does this symbol represent? What does this line represent? Reference: Ricki Lewis (2010), Lewis: Human Genetics: Concepts and Applications, Ninth Edition