BIO 305 1st Edition Lecture 4 Outline of Last Lecture I. PedigreesII. Extensions of Mendelian GeneticsIII. Different Types of DominanceIV. Blood-typesV. Multiple Gene InteractionOutline of Current Lecture I. Intro to Sex ChromosomesII. Morgan’s Experiment – Different Phenotypic Ratios Among SexIII. Bridges’ Experiment – Non-disjunction As Proof Of Chromosomal TheoryIV. Three Cases of Sex-Linked DiseasesV. Key Vocabulary and Sample QuestionsCurrent LectureI. Intro to Sex ChromosomesNotice: the human female karyotype’s 23rd chromosome consists of two X chromosomes and no Y chromosome, while the male has one X chromosome and one Y chromosome? This lecture will be about genes that are differentially transmitted on these chromosomesUnlike chromosomes contribute to sex determination:In drosophila (flies) and mammals: XX (Female) and XY (Male)homogametic vs. heterogametic (the focus of our studies in this course)In some other species: ZW (female) ZZ (male)although in this case, the female determination is heterogametic: the same rules apply!X-linkage - The Y-chromosomes do NOT contain homologous genes of the X chromosome, thus Xgenes exhibit a unique pattern of inheritanceException: Pseudoautosomal regions (PARs) – chromosomes that behave like autosomesII. Morgan’s Experiment – Different Phenotypic Ratios Among SexThomas H. Morgan – strongly influences both genetics and university education: spent 14 years studying drosophila and sex-linked geneticsWhy are drosophila good model organisms?Fecundity (which results in accurate ratios), short generations, easy care, andsimple karyotype: 3 autosomes and 1 sex chromosome (is observable, too)T. H. Morgan’s Experiment:Found that the distribution of phenotypes were different in male vs. female:Color of the eyes (white vs. red) were associated with the sex:P: When a red female crossed with a white maleF1: All redF2: All females were red, 1:1 ratio of white and red for malesP: But when a white female is crossed with a red maleF1: All females were red, all males were whiteF2: 1:1 ratio of white and red per sexResults suggested that the white gene is located on the X chromosome3 Rules: 1) Y is ALWAYS paternally transmitted2) For a male, the X comes from the mother: MOM  Son’s X3) For a female, receives an X from both parents: MOM + DAD  Daughter’s XXIII. Bridges’ ExperimentC. B. Bridges - repeated Morgan’s experiments and came up with Non-disjunction as proof of the chromosome theory of inheritance (more proof that genes are located ON chromosomes)P: Cross of white female with red maleF1: Saw a rare event in which .05 % had white eyesExplanation?1st division nondisjunction in oogenesis of an XX female resulted in XXY female fly progenies:¼ had XX/X, which is lethal in flies (not humans!) so they died¼ had X/0, which results in sterile males¼ had XX/Y resulted in white-eyed females, because the two X chromosomes came from the mother¼ had 0/Y, also lethalWhat if you cross a XXY female with a wild-type red-eyed male?Y randomly goes to one X cell - 84% of the time, all males are white16% - lethal for malesIV. Three cases of Sex-Linked DiseasesCASE ONE: Color-blindness – a gene mutation located on the X chromosomeThe pedigree is special because more males are affected – BOTH X chromosomes must have the mutation for the female to have the diseaseWhy?Males get the C or c allele from the mother, females are carriers because they get it from both mom and dadBiochemical explanation: Humans have 3 opsin genes to see color: red, green, blueIf one of these mutated, get color-blindness. The chromophore in the visual pigment of the eyes changes conformation with differing sensitivities to light.Thus, if you “fix” the mutation on the gene, this should fix the problem?Not necessarily: Gene therapy doesn’t always work because the brain is “trained” during development and doesn’t see color even if you get the right gene later in life: the ability to see color depends on the wiring of the brainCASE TWO: Hemophilia A in Royal Families – a bleeding disorder caused by lack of blood clottingfactor VIIITsar Nicholas was not a carrier, his genotype: XA YTsarina Alexandra was a carrier: XA XaAlexis, only brother of four sisters, has the disorder: XA YCASE THREE: Hypophosphatemia : Vitamin-D Resistant Rickets, an X-linked dominant diseaseX-linked dominant means that you only need one bad allele to get the diseaseIn the pedigree, you will notice that many are affected regardless of gender.If a male is affected, ALL daughters are affectedIf a female is affected, half the kids are affected (only one X from mom)V. ImprintingGenomic (Parental) Imprinting – a condition where the expression of a trait depends on whether the trait has been inherited from a male or female parentEx: Maternal Imprinting in Mice (think of it as “turn-offing”)Expected a 3:1 ratio but instead received a 1:1 ratio, because the heterozygous got turned off:There is imprinting on the normal allele inherited by the mother. The dwarf with the twomutant alleles was also turned off but was already a mutant, thus there was no effect for that individualMolecular basis? Methylation in the maternally contributed alleles but not the male alleles – the chemical modification of a geneIn the development of the germ-line, methylation imprint is erasedBut methylation is reestablished in oogenesis, but NOT spermatogenesis: thus, methylation will depend on whether the offspring is male or female, the gender of the parent who donated their allele does not matter in this caseKey VocabularyFecundity – capacity to produce lots of offspringHemizygotes – individuals with only one copy of a given geneNondisjunction – failure for homologous chromosomes to separate in MeiosisThese traits are on autosomes only, but phenotype pattern differs between sexes:Sex limited traits – traits observed in only one sex (only roosters can be cock-feathered)Sex influenced traits – traits observed in both sexes, but the expression of gene differsDominance relationship is different between male and female (BB is bald for females, but bb is bald for men: same gene though)The genotype is the same, but not the phenotype: environmentalPenetrance – percentage of individuals that show some degree of expression of a mutant genotypeExpressivity – range of expression of a mutant genotype (for example, 10 people have a mutation, but the degree of its severity differs)Ex: The