Figure 1: Transmission of Wing Shape & Body Color Alleles: F0 Mating. Figure 1.1: Transmission of Wing Shape & Body Color Alleles: Expected F1 Outcome
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1 I. Chromosomal Theory of Inheritance As early cytologists worked out the mechanism of cell division in the late 1800 s, they began to notice similarities in the behavior of BOTH chromosomes & Mendel s factors a) Chromosomes & alleles occur in pairs in diploid cells. b) Homologous chromosomes & alleles segregate during meiosis. c) Fertilization restores the paired condition for both chromosomes & alleles. It was later determined that these similarities were due to the fact that alleles RESIDE on chromosomes. As a result, chromosome behavior during division explains allele segregation & independent assortment. II. Gene Linkage American geneticist Thomas Hunt Morgan performed mating experiments with the fruit fly Drosophila melanogaster. Specifically, he traced the inheritance of two traits, body color & wing shape, across generations. Initially, Morgan crossed female dihybrids having gray bodies & normal wings: (b + b vg + vg) with double mutant males having black bodies & vestigial (flightless) wings (bbvgvg). Figure 1: Transmission of Wing Shape & Body Color Alleles: F0 Mating Figure 1.1: Transmission of Wing Shape & Body Color Alleles: Expected F1 Outcome According to Mendel s principle of independent assortment, Morgan s matings were expected to produce 4 phenotypic classes of F1 offspring, in approximately equal ratios: 1 gray-normal: 1 black-normal: 1 gray-vestigial: 1 black-vestigial.
2 Figure 1.2: Transmission of Wing Shape & Body Color Alleles: Observed F1 Outcome Instead of observing all 4 possible phenotypes in equal ratios, Morgan observed that the phenotypic ratios were not equal, but overwhelmingly skewed in favor of the parental phenotypes. To explain this outcome, Morgan concluded that alleles for body color & wing shape in Drosophila melanogaster were Linked, or found on the same chromosome Figure 1.3: Transmission of Wing Shape & Body Color Alleles: Gamete Formation Assuming Gene Linkage Figure 1.4: Transmission of Wing Shape & Body Color Alleles: Expected F1 Results Assuming Gene Linkage
3 If the genes for body color & wing shape are truly linked, one should expect to see nothing but the parental phenotypes in the F1 generation. Instead, we also see recombinants. This observation can be explained in that crossing over can unlink linked genes leading to new allele combinations. Figure 1.5: Transmission of Wing Shape & Body Color Alleles: Effects of Crossing Over Figure 1.6: Linked Genes & MAP Units Linked Genes: a) MAP UNITS (MU) =relative distance between loci on a chromosome; can be expressed as the frequency at which two loci on a chromosome can be separated by crossing over (closer the loci, the less likely crossing over will separate them).
4 III. Sex Chromosomes & Sex Linkage Figure 2: Chromosomal Basis for Gender Determination During fertilization, it is the sperm cell (X OR Y) that determines the gender of the child upon fusing with an ovum (X). If present in the resulting zygote, it is the Y chromosome that will direct its development into a male. If absent, the zygote will develop into a female. Figure 3: X-Linked Alleles: Drosophila Eye Color
5 Figure 3.1: X-Linked Alleles: Hemizygous Males In contrast, females would need to inherit TWO copies of the (w) allele to exhibit white eyes white-eyed females less frequent. Sex-Linked Genes: Figure 3.2: Generalized Sex-Linked (X) Inheritance Pattern Mutated X-linked alleles that cause disease are those associated with hemophilia & color-blindness (both more common among males).
6 IV. Genetic Disorders & Pedigree Analysis Figure 4: Sample Pedigree Pedigrees are models that can be used to determine the inheritance pattern of a trait in a family (or a large group of people) across multiple generations. Figure 5: Inbreeding & Frequency of Recessive Disorders Within isolated gene pools, mate choice is limited. Consequently, mating between related individuals is likely; since such individuals are likely to carry the same harmful alleles, mating between them is more likely to produce affected offspring. Over time, such deleterious recessive alleles are expected to increase in frequency within the gene pool (assuming it remains isolated). Examples of such harmful autosomal recessive alleles include those causing cystic fibrosis, tay sachs, & sickle-cell anemia Tay Sachs: 1 in 3600 births to Central & Eastern European Jews. Results from a mutation of a gene on chromosome 15. Brain cells of infected individuals are unable to produce an enzyme (Hex A) to metabolize lipids called gangliosides formed within the developing brain. If not broken down, these lipids will collect in the brain & disrupt mental & neural functions until the entire central nervous system stops working.
7 Cystic Fibrosis: 1 in 2500 Caucasian births. Results from a mutation in a gene on chromosome 7 that normally codes for a membrane protein (CFTR) that functions in Cl- transport between cells & the extracellular fluid. The channels are defective or absent in cystic fibrosis sufferers, resulting in an abnormally high extracellular Cl- concentration. This causes the mucus that coats certain cells to be thicker & stickier than normal. The mucus builds up in the lungs, pancreas, digestive tract & various other organs. Sickle Cell Anemia: 1 in 500 African births. Caused by a mutation resulting in the wrongful production of a single amino acid in the Hb protein. Upon releasing oxygen, the abnormal Hb proteins may cluster together to form rod-like structures, causing them to assume a sickle shape. Unlike normal red blood cells, which last about 120 days in the bloodstream, sickled red blood cells last days. Since they cannot be replaced fast enough, the blood is chronically short of red blood cells, a condition known as anemia. Blood transfusions can relieve the symptoms, although there is no cure. Figure 6: Autosomal Dominant Disorders: Huntington s Disease Alleles for dominant disorders (e.g. Huntington s allele) are extremely rare within populations & lethal in the homozygous condition. Thus, always assume that an individual affected by a dominant disorder to be heterozygous for the condition. Figure 7: Methods of Genetic Screening *Both methods can be used to assess the development of a fetus prior to birth through the production of a karyotype. The information provided by the karyotypes includes chromosome number, shape, & the presence of any deletions, inversions, translocations, or duplications.
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