5.1 - Haploid Versus Diploid Organisms

• Haploid(n) organism - Has only one copy of each type of chromosome. In humans, this refers to a cell that has one copy of each type of homologous chromosome.

• **Diploid (**2n) organism - Has two copies of each type of chromosome. In humans, this refers to the pairs of homologous chromosomes.

5.2 - Meiosis

• Meiosis - occurs during the process of sexual reproduction.

• A cell destined to undergo meiosis goes through the cell cycle, synthesizing a second copy of DNA.

• But after G2, the cell instead enters meiosis, which consists of two cell divisions, not one.

• The second cell division exists because the gametes to be formed from meiosis must be haploid.

• This is because they are going to join with another haploid gamete at conception to produce the diploid zygote. Two parts - meiosis I and meiosis II.

• Four steps, similar to mitosis: prophase, metaphase, anaphase, and telophase.

• Homologous chromosomes - resemble one another in shape, size, function, and the genetic information they contain.

• In humans, the 46 chromosomes are divided into 23 homologous pairs.

• One member of each pair comes from an individual’s mother, and the other member comes from the father.

• Meiosis I - the separation of the homologous pairs into two separate cells.

• Meiosis II - the separation of the duplicated sister chromatids into chromosomes.

• As a result, a single meiotic cycle produces four cells from a single cell. The cells produced during meiosis in the human life cycle - gametes.

  Steps of Meiosis I

• Prophase I - Each chromosome pairs with its homolog. Crossover (synapsis) occurs in this phase. The nuclear envelope breaks apart, and a spindle apparatus begins to form.

• Metaphase I - Chromosomes align along the metaphase plate matched with their homologous partner. This stage ends with the separation of the homologous pairs.

• Anaphase I - Separated homologous pairs move to opposite poles of the cell.

• Telophase I - Nuclear membrane reforms; the process of cytoplasmic division begins.

• Cytokinesis - After the daughter cells split, the two newly formed cells are haploid (n).

• Meiosis consists of a single synthesis period during which the DNA is replicated, followed by two acts of cell division.

• With the completion of the first cell division, meiosis I, the cells are haploid because they no longer consist of two full sets of chromosomes.

• The cell then enters meiosis II.

  Steps of Meiosis II

• Prophase II - The nuclear envelope breaks apart, and spindle apparatus begins to form.

• Metaphase II - Sister chromatids line up along the equator of the cell.

• Anaphase II - Sister chromatids split apart and are called chromosomes as they are pulled to the poles.

• Telophase II - The nuclei and the nucleoli for the newly split cells return.

• Cytokinesis - **Newly formed daughter cells physically divide

• Process of gamete formation:

• In men, spermatogenesis leads to the production of four haploid sperm during each meiotic cycle.

• In women- called oogenesis. Trickier process than spermatogenesis - each complete meiotic cycle leads to the production of a single ovum, or egg.

• After meiosis I in females, one cell receives half the genetic information and the majority of the cytoplasm of the parent cell.

• The other cell, the polar body, receives half of the genetic information and is cast away.

• During meiosis II, the remaining cell divides a second time, and forms a polar body that is cast away, and a single haploid ovum that contains half the genetic information and nearly all the cytoplasm of the original parent cell.

• The excess cytoplasm is required for proper growth of the embryo after fertilization.

  Stages of Meiosis

  

• **crossover/**crossing over - when the homologous pairs match up during prophase I of meiosis, complementary pieces from the two homologous chromosomes wrap around each other and are exchanged between the chromosomes.

5.3 - Some Important Terms to Know

• Allele: a variant of a gene for a particular character. For eg, two alleles for fur color could be B (dominant) and b (recessive).

• F1: the first generation of offspring, or the first “filial” generation in a genetic cross.

• F2: the second generation of offspring, or the second “filial” generation in a genetic cross.

• Genotype: an organism’s genetic makeup for a given trait. Eg: fur color - B represents the allele for brown and b represents the allele for black. The possible genotypes - homozygous brown (BB), heterozygous brown (Bb), and homozygous black (bb).

• Heterozygous (hybrid): an individual is heterozygous (or a hybrid) for a gene if the two alleles are different (Bb).

• Homozygous (pure): an individual is homozygous for a gene if both of the given alleles are the same (BB or bb).

• Karyotype: a chart that organizes chromosomes in relation to number, size, and type.

• Nondisjunction: the improper separation of chromosomes during meiosis, which leads to an abnormal number of chromosomes in offspring. Eg: nondisjunction-related syndromes - Down, Turner, and Klinefelter syndromes.

• P1: the parent generation in a genetic cross.

• Phenotype: the physical expression of the trait associated with a particular genotype. Eg: Mendel’s peas - round or wrinkled, green or yellow, purple flower or white flower.

5.4 - Sources of Cell Variation

• The process of cell division - ample opportunity for variation.

• During meiosis, homologous chromosome pairs align together along the metaphase plate.

• Completely random process - there is a 50 percent chance that the chromosome in the pair from the individual’s mother will go to one side, and a 50 percent chance that the chromosome in the pair from the individual’s father will go to that side.

• 2n possible gametes can form from any given set of n chromosomes.

• In humans, there are 23 homologous pairs - 223 (8,388,608) different ways the gametes can separate during gametogenesis.

• Another source of variation during sexual reproduction - the random determination of which sperm meets up with which ovum.

• In humans, the sperm - one of 223 possibilities from the male gamete factory; the ovum, one of 223 possibilities from the female gamete factory.

• Crossover another major source of variation.

• Happens only during that stage of cell division. It does not occur in mitosis.

5.5 - Mendel and His Peas

• Gregor Mendel - spent many years working with peas.

• He mated peas to produce offspring and recorded the phenotype results in order to determine how certain characters are inherited.

• Character a genetically inherited characteristic that differs from person to person.

• Before he began his work in the 1850s, the accepted theory of inheritance was the “blending” hypothesis - stating that the genes contributed by two parents mix as colors do.

• Mendel used plant experiments to test this hypothesis and developed his two fundamental theories: the law of segregation and the law of independent assortment.

• Monohybrid cross—a cross that involves a single character in which both parents are heterozygous (Bb × Bb).

• A monohybrid cross between heterozygous gametes gives a 3 : 1 phenotype ratio in the offspring.

• Dihybrid cross - the crossing of two different hybrid characters (BbRr × BbRr).

• A dihybrid cross between heterozygous gametes gives a 9 : 3 : 3 : 1 phenotype ratio in the offspring.

• The law of segregation - Every organism carries pairs of factors, called alleles, for each trait, and the members of the pair segregate (separate) during the formation of gametes.

• For example, if an individual is Bb for eye color, during gamete formation, one gamete would receive a B, and the other made from that cell would receive a b.

• The law of independent assortment - Members of each pair of factors are distributed independently when the gametes are formed. Inheritance of one trait or characteristic does not interfere with inheritance of another trait.

• For example, if an individual is BbRr for two genes, gametes formed during meiosis could contain BR, Br, bR, or br. The B and b alleles assort independently of the R and r alleles.

• The law of dominance - When two opposite pure-breeding varieties (homozygous dominant vs. homozygous recessive) of an organism are crossed, all the offspring resemble one parent. This is referred to as the dominant trait. The variety that is hidden - recessive trait.

• Phenotype of an organism - can be determined from simple observation.

• Genotype of an organism - cannot always be determined from simple observation.

• In the case of a recessive trait, the genotype is known.

• To determine the exact genotype - Experiment called test cross.

• Geneticists breed the organism whose genotype is unknown with an organism that is homozygous recessive for the trait.

• This results in offspring with observable phenotypes.

• If the unknown genotype is heterozygous, probability indicates one-half of the offspring should express the recessive phenotype.

• If the unknown genotype is homo-zygous dominant, all the organism’s offspring should express the dominant trait.

5.6 - Non-Mendelian Genetics

• Gregor Mendel’s work - not able to account for many patterns of inheritance that occur in life (sex-linked traits, incomplete dominance, and codominance).

• The observed phenotypes of these traits differ from the predicted ratios.

• Non-nuclear inheritance, in which offspring get DNA only from the male or female parent, does not follow the Mendelian pattern of inheritance.

5.7: Intermediate Inheritance

• intermediate inheritance - an individual heterozygous for a trait (Yy) shows characteristics not exactly like either parent.

• The phenotype is a “mixture” of both of the parents’ genetic input.

• Two major types of intermediate inheritance: incomplete dominance/blending inheritance, codominance.

  Incomplete dominance/Blending inheritance

• The heterozygous genotype produces an “intermediate” phenotype rather than the dominant phenotype; neither allele dominates the other.

• Genetic condition in humans that exhibits incomplete dominance - hyper-cholesterolemia—a recessive disorder (hh) that causes cholesterol levels to be many times higher than normal and can lead to heart attacks in children as young as 2 years old.

• The environment plays a major role in how genetic conditions express themselves.

  Codominance

• Both alleles express themselves fully in a heterozygous organism.

• Example - human blood groups: M, N, and MN.

• Individuals with group M blood have the M glycoprotein on the surface of the blood cell; individuals with group N blood have N glycoproteins on the blood cell; and those with group MN blood have both.

• This is not incomplete dominance because both alleles are fully expressed in the phenotype—they are codominant.

5.8: Other Forms of Inheritance

Polygenic Traits

• Traits that are affected by more than one gene.

• Example - eye color.

• The tone (color), amount (blue eyes have less than brown eyes), and position (how evenly distributed the pigment is) all **play a role in determining eye color.

• Another example - skin color.

  Multiple Alleles

• Many monogenic traits (traits expressed via a single gene) correspond to two alleles, one dominant and one recessive.

• Other traits, however, involve more than two alleles.

• Example - the human blood type.

Epistasis

• The expression of one gene affects the expression of another gene.

• Example - the coat color of mice.

  Pleiotropy

• A single gene has multiple effects on an organism.

• Example - the mutation that causes sickle cell anemia.

• This single gene mutation “sickles” the blood cells, leading to systemic symptoms such as heart, lung, and kidney damage; muscle pain; weakness; and generalized fatigue.

5.9 - Sex Determination and Sex Linkage

• Thomas Morgan made key discoveries regarding sex linkage and linked genes.

• Sex chromosomes - X and Y.

• Women have two structurally identical X chromosomes. Men have one X and one Y.

• Morgan experimented with a quick-breeding fruit fly species.

• The fruit flies had four pairs of chromosomes: three autosomal pairs and one sex chromosome pair.

• Autosomal chromosome - not directly involved in determining gender.

• Wild-type phenotype - the more common phenotype for a trait.

• Mutant phenotype - traits that are different from the normal.

• Morgan crossed a white-eyed male with a red-eyed female, and all the F1 offspring had red eyes.

• When he bred the F1 together, he obtained Mendel’s 3:1 ratio.

• Slight difference - the white trait was restricted to the males.

• Morgan’s conclusion - the gene for eye color is on the X chromosome.

• Male–female sex chromosomes difference - allows for sex-linked conditions.

• If a gene for a recessive disease is present on the X chromosome, then a female must have two defective versions of the gene to show the disease while a male needs only one.

  Common Sex-Linked Disorders

• Duchenne’s muscular dystrophy Caused by the absence of an essential muscle protein. Symptoms - progressive loss of muscle strength and coordination.

• Hemophilia caused by the absence of a protein vital to the clotting process. Individuals with this condition have difficulty clotting blood **after even the smallest of wounds. Those most severely affected by the disease can bleed to death after the tiniest of injuries.

• Red-green colorblindness individuals with this are unable to distinguish between red and green colors; found primarily in males.

  X Inactivation

• Females undergo a process called X inactivation.

• During the development of a female embryo, one of the two X chromosomes in each cell remains coiled as a Barr body whose genes are not expressed.

• A cell expresses the alleles only of the active X chromosome.

• X inactivation occurs separately in each cell and involves random inactivation of one of a female’s X chromosomes. But not all cells inactivate the same X. As a result, different cells will have different active X chromosomes.

• One last sex-related inheritance pattern that needs to be mentioned is holandric traits, which are traits inherited via the Y chromosome. Example - ear hair distribution.

5.10 - Linkage and Gene Mapping

• Linked genes - genes that tend to be inherited together because the chromosome is passed along as a unit.

• Lie on the same chromosome; do not follow Mendel’s law of independent assortment.

• Morgan performed an experiment in which he looked at body color and wing size on fruit flies.

• The dominant alleles were G (gray) and V (normal wings); the recessive alleles were g (black) and v (vestigial wings).

• GgVv females were crossed with ggvv males.

• Mendel’s law of independent assortment predicts offspring of four different phenotypes in a 1:1:1:1 ratio.

• But because the genes are linked, the gray/normal flies produce only GV or gv gametes.

• Thus, Morgan expected the ratio of offspring to be 1:1, half GgVv and half ggvv.

• Morgan found that there were more wild-type and double-mutant flies than independent assortment would predict, but some Gv and gV were also produced.

• Crossover - a form of genetic recombination that occurs during prophase I of meiosis, led to their production.

• Recombination frequency can be used to determine how close two genes are on a chromosome through the creation of linkage maps.

  Linkage Maps

• Genetic map put together using crossover frequencies.

• Another unit of measurement, the map unit (also known as centigram), is used to geographically relate the genes on the basis of these frequencies.

• One map unit - equal to a 1 percent crossover frequency.

• Does not provide the exact location of genes; it gives only the relative location.

5.11: Heads or Tails?

• Law of multiplication states that to determine the probability that two random events will occur in succession, you simply multiply the probability of the first event by the probability of the second event.

• Mendel’s law of segregation - If you are Aa for a trait, your chance of passing on the A—1⁄2. If you are AaBb, the chance you pass on both A and B- multiply 1⁄2 × 1⁄2 to get 1⁄4.

5.12: Pedigrees

• Pedigrees family trees used to describe the genetic relationships within a family.

• Squares - represent males; circles - females.

• A horizontal line from male to female represents mates that have produced offspring.

• Usage of pedigrees: determine the risk of parents passing certain conditions to their offspring.

5.13 - Common Disorders

• Tay-Sachs disease - fatal genetic disorder that renders the body unable to break down a particular type of lipid that accumulates in the brain and eventually causes blindness and brain damage.

• Individuals with this disease typically do not survive more than a few years.

• This disease is found in a higher-than-normal percentage of people of eastern European Jewish descent.

• Cystic fibrosis (CF) - recessive disorder, the most common fatal genetic disease in the US.

• The normal allele for this gene is involved in cellular chloride ion transport.

• A defective version of this gene results in the excessive secretion of a thick mucus, which accumulates in the lungs and digestive tract.

• Statistically, 1 in 25 Caucasians is a carrier for this disease.

• Sickle cell anemia a common recessive disease that occurs as a result of an improper amino acid substitution during translation of hemoglobin.

• Results in the formation of a hemoglobin protein that is less efficient at carrying oxygen.

• It also causes hemoglobin to deform to a sickle shape when the oxygen content of the blood is low, causing pain, muscle weakness, and fatigue.

• Sickle cell anemia is the most common inherited disease among African Americans.

• Phenylketonuria (PKU) - autosomal recessive disease caused by a single gene defect.

• Children with PKU are unable to successfully digest phenylalanine (an amino acid).

• Leads to the accumulation of a by-product in the blood that can cause mental retardation.

• If the disease is caught early, retardation can be prevented by avoiding phenylalanine in the diet.

• Huntington disease - A fatal disease that causes the breakdown of the nervous system.

• It does not show itself until a person is in their 30s or 40s, and individuals afflicted with this condition have a 50 percent chance of passing it to their offspring.

5.14 - Chromosomal Complications

• Nondisjunction an error in homologous chromosome separation. It can occur during meiosis I or II. The result is that one gamete receives too many of one kind of chromosome, and another gamete receives none of a particular chromosome. The fusing of an abnormal gamete with a normal one can lead to the production of offspring with an abnormal number of chromosomes (aneuploidy).

• Down syndrome affects 1 out of every 700 children born in the US. It most often involves a trisomy of chromosome 21, and leads to mental retardation, heart defects, short stature, and characteristic facial features. Most people with trisomy 21 are sterile.

• Patau syndrome - causes serious brain and circulatory defects; trisomy 13.

• Edwards syndrome - can affect all organs; trisomy 18.

• Klinefelter syndrome (XXY) - infertile individuals, have male sex organs but show several feminine body characteristics.

• Turner syndrome (XO) - sterile females who possess sex organs that fail to mature at puberty.

• Deletion - occurs when a piece of the chromosome is lost in the developmental process.

• cri-du-chat syndrome - occurs with a deletion in chromosome 5 that leads to mental retardation, abnormal facial features, and a small head.

• Chromosomal translocations - A piece of one chromosome is attached to another, nonhomologous chromosome, can cause major problems.

• Chronic myelogenous leukemia a cancer affecting white blood cell precursor cells. In this disease, a portion of chromosome 22 has been swapped with a piece of chromosome 9.

• Chromosome inversion - occurs when a portion of a chromosome separates and reattaches in the opposite direction. This can have no effect at all, or it can render a gene nonfunctional if it occurs in the middle of a sequence.

• Chromosome duplication - results in the repetition of a genetic segment.