jimtrue.com : school : BSC2010 : CH 14 & 15: Mendel & the Gene Idea - Chromosomal Basis of Inheritance

Posted by Jim True on April 1, 2004 6:43 AM. Last Updated October 22, 2006 9:23 PM

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CH 14 & 15: Mendel & the Gene Idea - Chromosomal Basis of Inheritance

Genetic Terms & Concepts

• Character -- any variable, inheritable feature.
• Trait -- Any variant of a character.
• Allele -- One of two or more alternate states of a gene at a specific locus.
• Homozygous -- Both alleles on a homologous chromosome pair are identical.
• Heterozygous -- Alleles on a homologous chromosome pair are different.
• True-Breeding -- All offspring exhibit the same trait, thus, alleles are homozygous for the trait.
• Hybrid -- Crossing of true-breeding individuals for one ("monohybrid"), two ("dihybrid") or more traits.
• Dominant -- The allele that produces the observed trait IN A HETEROZYGOTE. The allele is indicated by a capital letter.
• Recessive -- The allele whose trait is hidden IN A HETEROZYGOTE. The allele is indicated by the SAME letter as the dominant, but in lower case.
• P (Parental) generation -- The original true-breeding individuals for the trait(s) being studied.
• F₁ (first filial) generation -- The hybrid offspring from the P generation. These may be monohybrids, dihybrids, etc.
• F₂ (second filial) generation -- The offspring from the F₁ generation, which was the mono- or dihybrid, etc. CROSS.
• Phenotype -- The specific PHYSICAL or CHEMICAL expression of a gene.
• Genotype -- The genetic makeup for an individual (or for a specific phenotype).
• Punnett Square -- A "shorthand" method for predicting results of a cross between individuals of a known genotype. This is mainly useful for mono- and dihybrid crosses.

Mendel and Heredity

• Gregor Mendel was an Austrian monk who lived during the 1800's.
• he is considered the "father" of modern day genetics because of work he first published in 1865.
• He was NOT the first person to observe variability in populations or that characteristics could be passed from generation to generation.
• He was the first person to QUANTIFY his results and show that many inherited characteristics were inherited in a specific, PREDICTABLE pattern!
• His conclusions are all the more powerful when one considers that he published his results BEFORE the discoveries of chromosomes, genes, alleles, DNA and meiosis!
• Mendel performed his work on garden peas. There were a number of reasons why pea plants were an excellent study choice:
  1. Easily grown.
  2. Short lived (could examine several generations per year)
  3. Had many characteristics that were readily observable.
  4. The characteristics selected had two distinguishable states ("either or" traits).
  5. Could be self-fertilized. This could ensure that "true breeding" (homozygous) conditions could be produced.
• Mendel examined 7 different traits (Table 14.1, p. 250). It turns out that each of these happen to only have two alleles for each trait, and one allele is truly dominant and the other is truly recessive.

The Law of Segregation

• Before Mendel's work, a common conception was that inheritance was BLENDED, that is, offspring exhibited a mixture of the parental trait. Mendel tested this concept using single traits.
• Mendel's First Law Experiment --
  1. Select a specific characteristic, eg. flower color. Two colors, purple and white.
  2. Ensure that plants self-fertilize for several generations to create "true breeding", ie, offspring of purple plants always produce purple flowers, and white offspring only from white plants.
  3. Cross one true breeding plant for one characteristic with a true breeding plant for the (P or "parent" generation).
  4. Record the number of offspring (F₁ or "first filial" generation) and the characteristics observed.
  5. Cross two F₁ plants. Record the number of offspring (F₂ or "second filial" generation) and characteristics.
• Mendel's First Law Results --
  1. The cross of the two traits in the P generation produced F₁ offspring with only ONE trait. Plants did NOT produce intermediate offspring indicating that inheritance was NOT blended.
  2. For each pair of traits examined, one was NOT expressed in the F₁ generation but did not show up in the F₂ generation.
  3. If characteristic was not present in F1 but could show up in F2, then it must have been HIDDEN in the F1 generation, not lost.
  4. Alternate characteristics reappeared in the F2 generation, some offspring showing one trait, some showing the other.
  5. In the F2 generation, the alternative traits would be expressed in a ratio of 3:1, that is, 75% of the spring would look like the parents (F1).
• In modern terms -- F1 offspring all show dominant trait, F2 show a 3:1 dominant:recessive PHENOTYPE ratio.
• The 3:1 ratio is called the Mendelian ratio for a MONOHYBRID cross.
• The genotype ratio for such a cross is 1:2:1 homozygous dominant:heterozygous:homozygous recessive. If given question for ratio; don't just put down numbers, MUST explain the reason for the numbers. (p. 252 figure 14.5)
• These are not actual numbers but PROBABILITIES of outcomes.
• Mendel's work on this aspect of genetics led to a hypothesis that has ultimately come to be known as Mendel's First Law of Genetics -- The Law of Segretation (separation).
• Expressed in modern terms, the law states:
  1. Alternative forms of a trait (variable characteristics) are specified by alternative alleles that DO NOT BLEND in a heterozygote.
  2. Each offspring inherits two alleles, one from each parent.
  3. If the two alleles differ in the offspring, only the dominant allele is expressed. The recessive is in no way altered, its expression is simply hidden.
  4. When 2n heterozygote cell forms n gametes, alternative alleles SEGREGATE from one another (one in each gamete), hence the name of the law. Diploid cells pass traits randomly to haploid cells. Prefer to refer to this Law as Law of Segregation as opposed to Mendel's First Law of Genetics.

Test Cross

Mendel doesn't know anything about these factors -- how could he figure out homozygous as opposed to heterozygous.

• Mendel did not know about genes and called dominant and recessive alleles "inhertiable factors".
• How was he able to determine that a plant showing the dominant trait was "true breeding" and did not posses both "factors"?
• He developed a simple way of determining the allelic condition for a dominant phenotype.
• Test Cross -- (or a back cross), A method for testing whether an unknown dominant phenotype is homozygous or heterozygous. (Figure 14.6, p.252)
• Cross the unknown with with a recessive phenotype (which MUST be homozygous!).
• If unknown dominant is HOMOZYGOUS, resulting offspring will ALL be heterozygous (exhibit the dominant phenotype).
• If unknown dominant is HETEROZYGOUS, then the offspring will show a 1:1 ratio of dominant and recessive phenotypes. 50% chance of likely outcome.

Independent Assortment

• Once Mendel determined that "factors" (alleles) segregated from each other, he questioned whether genes would do the same thing, i.e, could different genes be inherited independently of one another or always in the same combination?
• Tested his ideas using a dihybrid cross, crossing individuals for two different genes (two different sets of traits) at once. (figure 14.7, p 253) If he had purple flowed plants would the purple always be tall, or would the traits inherit independently?
• His experimental setup followed the same design as his monohybrid crosses, except he tracked the progress of TWO different characters (e.g. flower color and plant height or pea color and pea texture).
• Mendel's Second Law Results --
  1. F₁ offspring all exhibited both traits of one true-breeding plant (ie, the heterozygous offspring showed only the dominant traits). First generations of true-breeding, are heterozygotes now, but only demonstrating dominant traits.
  2. F₂ generation exhibited
  a mix of traits in a 9:3:3:1 phenotype ratio, now called the Mendelian ratio for a dihybrid cross.
• These traits (phenotypes) were mixed as follows:
  • 9/16 both dominant traits expressed
  • 3/16 first trait dominant, second recessive
  • 3/16 first trait recessive, second dominant
  • 1/16 both recessive traits expressed.
• From these findings, Mendel concluded that "factors" for different characters do NOT directly affect each other.
• The hypothesis tested and supported by these experiments led to the establishment of a second basic law of genetics.
• Mendel's Second Law (The Law of Independent Assortment) -- Expressed in modern terms, this law states that different genes assort independently of one another on chromosomes and so do not directly influence each other.
• True for the most part because:
  • a) Different genes lie some distance apart on chromosome.
  • b) Genes lie on different chromosomes.
• This is not always the case, if two genes lie very closely together on same chromosome, they will likely NOT assort independently of one another.

Probabilities

• As mentioned, Mendelian ratios do not represent ACTUAL offspring numbers, but PROBABILITIES of outcome.
• The probability scale ranges from 0 to 1, which equals the percentage likelihood of an outcome, i.e., 1 = 100% change, 0 = 0% chance, and fractions equal some intermediate percentage.
• E.g. in the Mendelian monohybrid genotype ratio of 1:2:1, the Probability of a heterozygous genotype is 2/4 or 1/2 or 50%.
• Genetic cross probabilities are ruled by two laws of probability (just as in games of chance) (figure 14.8, p.254)
  • Rule of Multiplication -- Used to determine the chance that two or more independent events will occur together in a specific combination.
    • For genetics, the independent events are allele combinations.
    • It is determined by the MULTIPLICATION of the individual probabilities for each event. ie 1/2 x 1/2 = 1/4.
    • Example, what is the probability that in a cross of two heterozygotes (Pp x Pp), the offspring will have a Pp genotype?
    • Each gamete will have one of two allele possibilities (1/2P, 1/2p or 50%P, 50%p).
    • Each parent contributes one allele to the offspring (1/2P from father x 1/2P from mother).
    • Thus, offspring has a 1/4 chance (25%) of having PP genotype.
  • Rule of Addition -- This is used to determine the probability that the SAME event will be produced in different ways.
    • The individual probabilities are ADDED together.
    • Example -- what is the probability that in a cross of two heterozygotes (Pp x Pp), the offspring will have a Pp genotype?
    • As before, each gamete will have one of two allele possibilities (1/2P, 1/2p, or 50%P, 50%p).
    • Again, each parent contributes one allele to the offspring (1/2P from father x 1/2P from Mother).
    • However, we find that there is the probability that the father's P and the mother's p can combine in one outcome, and the father's p and the mother's P in a second outcome, each of which has a 1/4 probability.
    • Thus, 1/4 + 1/4 = 1/2 or 50%.
  • These two rules can be used in combination to quickly determine the probability of an outcome.
  • Useful in complex, multiple hybrid crosses.

Other Genetic Interactions

• The high degree of variability observed in sexually reproducing organisms can not be accounted for by Mendel's heredity principles alone, which basically accounted for random fertilization (via segregation of alleles) and independent assortment. Mendel's Laws have not been violated, but there have been advancements and variances to the laws.
• In fact, since Mendel's work a large number of gene interactions have been discovered that account for the variability among different population of living organisms.
  1. Crossing Over (Ch 15) -- This alone introduces great variability in the genetic makeup of an organism. (figure 15.5a, p.274)
  2. Sex Linked Trait (Ch 15) -- In organisms that possess sex chromosomes, females have two similar sex chromosomes, whereas males have two dissimilar chromosomes. In humans, we call these the X and Y chromosomes; females are XX, Males, XY. (figure 15.3, p.272) The Y chromosome has few functional genes. The genes present help to determine "maleness".
     • If an x chromosome pairs with another x, the dominant/recessive nature of the alleles dictates the expression.
     • But if an x pairs with a y, whatever alleles are on the x are expressed in the male offspring.
     • What if the x has a DEFECTIVE allele?
     • If paired with a normal allele on the second x chromosome, the female offspring will be a carrier for the defect but will not herself exhibit the defect.
     • If the defective x is paired with a y, the male offspring WILL have the defect.
     • Thus, the sex chromosomes determine the trait. (often called the x linked trait)
     • Examples of human sex linked traits are red-green color blindness and hemophilia (inability of the blood to clot).
     • Sex linked traits are primarily found in males, only very rarely in females.
  3. Incomplete Dominance (Ch 14) -- The dominant allele fails to completely hide the recessive, so a heterozygote exhibits a THIRD phenotype.
     • This often happens with flower color. (figure 14.9, p.256)
  4. Multiple Alleles and Co-Dominance (Ch 14) -- A 2n cell can only have a maximum of two different alleles, but there may be more than two alleles for a particular gene.
     • Example is human blood type, which has 3 alleles: IA, IB, iO. (Figure 14.10, p.257)
     • IA & IB are dominant, iO is recessive.
     • In individual, IAiO or IAIA is blood type A.
     • If alleles are IBiO or IBIB, blood type is B.
     • Only alleles iOiO produce blood type O.
     • Since IA and IB are BOTH dominant alleles, if we have the combination IAIB, then the blood type is AB, since both are expressed equally.
  5. Pleiotropy (ch 14) -- A single allele can produce more than a single phenotype.
     • An example is the human recessive genetic disorder known as sickle cell anemia. (figure 14.15, p 262)
     • In a homozygote for the condition, symptoms produced by the alleles can range from general anemia to extreme pain and organ damage from clumping of sickle cells to death.
  6. Multiple Genes and Polygenic Inheritance (Ch. 14) -- Several genes act in sequence or jointly to produce phenotype.
     • An example is human skin color. Three genes, each with an allele pair are involved (figure 14.12, p. 259)
     • Polygenic characters are usually referered to as quantitative (or continuous variation) because variations occur along a continuum. height, weight, hair color, eye color, head shape.
  7. Polygenic Inheritance and Epistatis (ch 14.11) -- The presence of certain alleles at one locus can prevent gene expression of alleles at a completely separate locus.
     • Example is albinism (the inability of the organism to produce the black-brown pigment melanin). (figure 14.11, p. 258)
     • Results from one homozygous recessive gene that affects a second gene.
  8. Environmental effects (Ch 14) -- many phenotypes are influenced by environment in the degree of expression.
  9. For any given genotype, there is a norm of reaction, that is, a range of responses that will be influenced to a variable extent by environment (e.g. weight range based on nutritional state).
  10. The range is widest for polygenic characters. (figure 14.13, p 259)

Human Genetics

• Genetic inheritances in humans, like other living organisms, often follow Mendelian Law.
• Pedigree (Ch 14) -- interrelationships of an organism through generations.
  • Allows one to determine possibilities of genetic outcomes, which is especially important in the case of genetic disorders, conditions that result due to the transmission of defective genes from one generation to another (figure 14.14, p. 261).
  • Many genetic disorders often involve a single gene locus and a defective allele and their interactions follow Mendel's laws.
  • Thus we can characterize many genetic disorders as dominant or recessive based on which allele is defective.
• Autosomal Recessive -- In order for the disorder to be present, the individual must be homozygous recessive. Any of the 22 non-sex chromosomes (not x or y linked) for humans.
  • Abinism -- pigment production is absent. Epistatis. Weak visual abilities, sensitive to light, burn easily, possibly skin cancer.
  • Sickle Cell Anemia -- hemoglobin in red blood cells is deformed. Results in varying responses as already discussed.
  • Phenylketonuria (PKU) -- Results in lack of a certain enzyme that converts the amino acid phenylalanine to a.a. tyrosine.
    • Instead, phenylalanine is converted to toxic substances which can destroy the central nervous system (results in retardation, death).
  • Tay-Sachs -- Causes progressive neurological disfunction & death by age 5.
    • Results from the absence of an enzyme that causes the breakdown of certain membrane lipids in the brain. Lipids build up and coat the neurons that trigger the chemical symbols, blocking the nervous system communication.
  • Cystic fibrosis (CF) -- causes abnormal levels of secretions from secretory cells in the body. Respiratory and intestinal tracks.
    • Especially severe in the respiratory system. Cells produce extremely thick mucus that cilia of the system can't clear.
    • Individuals can develop severe bacterial infections, resulting in often fatal pneumonia. Difficulties in breathing.
    • Thick mucus can also block liver and pancreatic functions, so there are numerous digestive problems as well. Doesn't allow enzymes to travel from the pancreas or bile to travel from the liver.
    • Some antibiotic treatments are helpful but few CF sufferers live beyond their 20's.
  • Traditionally, any autosomal recessive defects are associated with specific races or portions of populations. This is not always the case these days, because the races are more mixed these days and populations are not as isolated as they used to be.
  • PKU & CF -- Caucasians of Western European descent.
  • SCA -- African-Americans.
  • T-S -- Descendents of Eastern European (Ashkenazi) Jews.
  • Why? Because traditionally they marry within their culture or their population. Societal and religious edicts also keep the gene pools within a particular population.
• Autosomal Dominant -- Relatively few serious disorders of this type. (Dwarfism is an Autosomal Dominant, non-lethal).
  • The most severe is Huntington's Disease (Chorea). (So little control of their limbs, 'chorea' 'choreographer' -- looks like their dancing. Involves progressive disintegration of the brian, along with resultant convulsions, delusions, personality changes and ultimately death.
  • Typically exhibits a late onset, no symptoms until late 20's or 30's.
• Multifactorial Disorders -- Disorders or diseases that often involve not only alleles but one or more environmental factors as well.
  • Allelic interactions are often polygenic.
  • Examples include alchoholism, diabetes, certain types of schizophrenia and manic-depression.
• Genetic disorders may also result not from allelic alterations, which generate genetically inheritable disorders, but also in chromosomal abnormalities.
  • Nondisjunction -- Failure of chromosomes to separate during anaphase in meiosis. Extra or fewer chromosomes are passed to offspring. Disjunction is separation; non-disjunction means chromosomes did not separate. (figure 15.11, p.279) [ memorize this diagram ]
    • Nondisjunction in one or more chromosome pairs may occur during:
      • Anaphase I -- all gametes will be affected
      • Anaphase II -- 50% of gametes affected
    • Nondisjunction events are "mechanical accidents", most often related to the age of the gonadal cells, especially in females.
    • The results are never produced by defective genes and therefore, are not INHERITABLE problems!
    • Aneuploidy -- an abnormal number of chromosomes present in the cell.
    • Nondisjunction can affect either autosomes or sex chromosomes, producing distinctive genetic disorders or a lethal condition.
    • If lethal, the embryo does not develop to termal or at all. Female spontaneously aborts ("miscarries").
    • In humans, there are 23 pairs of chromosomes, numbered 1-23 and arranged in seven groups labeled A-G.
    • In the developing embryo, all 23 pairs must be present for proper development.
    • As a result of nondisjunction in humans, GAMETES will have either 0 or both of a particular chromosome (aneuploidy).
    • Aneuploidy will be present in one of two forms:
      • Monosomy -- If the gamete with 0 of a chromosome fertilizes (or is fertilized by) a normal gamete, only 1 of that chromosome is present in the offspring.
        • The cell has a 2n-1 condition for the affected chromosome(s).
        • The monosomic condition is typically lethal.
      • Trisomy -- If the gamete with 2 of a chromosome fertilizes (or is fertilized by) a normal gamete, then 3 of that chromosome are present in the offspring.
        • the chromosome count is 2n + 1 for the affected chromosome(s).
        • Trisomic condition can be lethal, but typically produces some abnormality in the offspring.
    • Polyploidy -- When entire sets of chromosomes undergo non-disjunction, generating multiple sets of chromosomes in the offspring (e.g. triploid or tetraploid counts).
      • Polyploidy often occurs among plant species, but is much less common in the animal kingdom although it is possible.
      • Polyploid individuals typically appear normal but may be sterile.
  • Other chromosomal abnormalities can be caued by such things as:
    • Deletions - Part of a chromosome is missing.
      • e.g. Cri-du-chat syndrome, a portion of chromosome 5 is missing, individuals cry like a kitten and exhibit mental retardation. French for 'cry of the cat'
    • Duplication -- Part of a chromatid attaches to the rest of the chromosome by a thin strand of DNA, called a fragile site.
      • the location of the fragile site is the same in all cells of an individual as well as affected members of the individuals family.
      • E.g. Fragile X syndrome -- Fragile site is near the tip of the x chromosome. Results in learning and attention disabilities to hyperactivity in males, females only rarely exhibit problems.
    • Inversion -- Portions of chromosome temporarily separate and then rejoin backwards. Alters gene loci.
    • Translocation -- Part of one chromosome breaks off and is joined to another different (non-homologous) chromosomes.
      • E.g. Part of chromosome 21 translocating to chromosome 14.
      • Translocated 14/21 causes an INHERITABLE form of Down syndrome. Aneuploidic trisomic down's is the non-inheritable form. Typically in older females.
      • aneuploidies include:
        • Autosomal Nondisjunction -- Occurs at one or more pairs of chromosomes 1-22.
        • Autosomal monosomy is invariably lethal: the embryo does not survive.
        • autosomal trisomy can produce several different outcomes:
          • Lethal Condition
          • Trisomy of some chromosomes (13, 15 and 18) may result in ??.
          • Trisomy on autosomes 21 or 22 result in varied conditions collectively known as Down's Syndrome.
        • A syndrome is a pattern of signs and symptoms always associated with a particular condition.
        • Person born with DS can display many varied symptoms.
        • Mental retardation of varying degrees, physical impairments, especially of vision, respiration and heart, and a higher incidence of certain cancers.
        • Leukemia is common in many DS individuals because the gene causing it is on autosome 21.
        • Many DS individuals have distinctine features.
        • Most DS individuals have distinctive features.
        • Most DS individuals die young. Some live to be adults, but very few reach "old age".
      • Sex Chromosome Nondisjunction -- Includes both monosomic and trisomic outcomes at fertilization.
        • Monosomy produces X- (or X0) or Y- (Y0) chromosome arrangement.
        • An X-individual exhibits a condition known as Turner's syndrome (TS).
        • The TS individual is female.
        • Most common signs are short stature, webbing of the neck, immature sex organs and infertility.
        • Some of the conditions (height, development of sex organs) can be treated with hormone therapy.
        • The monosomic Y- (Y0) condition is lethal.
        • Sex chromosome trisomy can produce xxx, xxy or xyy combinations.
        • xxx - produces a "metafemale". Produces a female with limited fertility and irregular menstrual cycles.
        • xxy -- results in Klinefelter's syndrome. Individual is typically a sterile male. May also exhibit feminine body characteristics, social, learning & coordination problems.
        • Like TS, KS can be treated with hormone therapy.
        • KS can also be exhibited in tetra- or pentaploid combinations of sex chromosome nondisjunctions (xxyy, xxxy, xxxxy, xyxxy).
        • xyy -- produces males with jacob's syndrome, taller than average, usually have acne.

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