CHAPTER 4:MODIFICATIONS OF MENDELIAN GENETICS4.1 Alleles Alter Phenotypes in Different Ways- Alleles are alternative forms of the same geneso Wild-type allele is the one that occurs more frequently in a population (designated as normal)- Mutation is the source of alleleso A mutant allele contains modified genetic information and often specifies an altered gene product- New Phenotypes (due to mutations) result from changes in functional activity of the cellular product specified by that geneo Mutations may: Change overall enzyme shape and thus reduce/ eliminate affinity for the substrate (Loss-of-function mutation) Cause complete loss of function (Null allele) May enhance allelic function (Gain-of-function mutations)- Usually result in dominant alleles since one copy in a diploid organism is sufficient to alter the normal phenotype Not show any change in function (Neutral mutation)4.2 Geneticists Use a Variety of symbols for Alleles- The initial letter of the name of a recessive trait, lowercased and italicized, denotes the recessive allele and the same letter in uppercase refers to the dominant allele- In Drosophila Melanogaster, an initial letter or combination of two-three letters of the name of the mutant is usedo Ex: Body color Ebony mutant is indicated by e Normal gray (Wild-type) is indicated by e+ e+/e+ or e+/e wild type e/e mutant If no dominance exists between alleles, italic uppercase italic letters and superscripts are used to denote alternative alleles ( R^1,R^2, C^W,C^R) The “/” indicates the two allele designations represent the same locus on two homologous chromosomes- Many diverse systems of genetic nomenclature are used to identify genes in various organisms- The symbol used should reflect the function of the gene or even a disorder caused by the geneo Yeast cdk represents the cyclin dependent kinase gene whose productis involved in cell-cycle regulationo In bacteria, leu- refers to a mutation that interrupts the biosynthesis of the amino acid leucine, and the wild-type gene is designated leu*o The symbol dnaA represents a bacterial gene involved in DNA synthesiso In humans, capital letters are used to name genes: BRCA1, the gene associated with breast cancer4.3 Neither Allele is Dominant in Incomplete, or Partial, Dominance- A cross between parents with contrasting traits may generate offspring with an intermediate phenotype in the heterozygote (Incomplete or Partial dominance)o Red snap dragons X white snapdragons F1 is all pinko Pink X Pink 1 Red : 2 Pink : 1 Whiteo The phenotypic ratio is identical to the genotypic ratio o Neither trait is dominant in incomplete dominance (no uppercase or lower case, use subscript C^R) C^R = red C^W = Whiteo Offspring from a cross between parents with contrasting traits may have a intermediate phenotype- Tay-Sachs disease in humanso Homozygous recessive die from fatal lipid-storage disorder, when hexosaminidase activity is absent in individualo Heterozygotes have only a single copy of the mutant gene and are phenotypically normal, but have only 50 percent of the enzyme activity found in homozygous normal individuals4.4 In Codominance, the Influence of Both Alleles in a Heterozygote is Clearly Evident- Codominance - joint expression of two alleles of a gene in a heterozygote results in phenotypic detection of both gene productso Inheritance in which two alleles of a gene pair in a heterozygote both have full phenotypic expression- Codominant inheritance is characterized by distinct expression of the gene products of both alleles- The MN blood group in humans illustrates Codominance o Genotype Phenotypeo LMLM Mo LMLN MNo LNLN N- A mating with two heterozygotes may produce children with all three blood types 1:2:14.5 Multiple Alleles of a Gene May Exist in a Population- Mutations modify the information stored in any gene by producing different alleleso For any specific gene, there can be more than two alleles within members of a population o Multiple alleles refer to three or more alleles of the gene (create unique mode of inheritance) Can only be studied in populations , not individuals- Human ABO blood groups provide an example of multiple alleles in a populationo The ABO system exhibits the codominant mode of inheritanceo 4 phenotypes are present A, B, AB, Oo I^A and I^B are responsible form making their respective A and B antigens and I is an allele that does not produce either antigens- I^A alleles are in the nucleus- I^A gene products are in the golgi- “A” antigens are on the cell surface- The Bombay Phenotypeo A woman was typed as type O but: One parent was AB blood and she passed the I^B allele to her childreno A and B antigens are derived from aprecursor molecule, H Substance o In the Bombay Phenotype The H substance isincompletely formed and thus: No antigens were formed Type O was expressed (BombayPhenotype) Even with I^A, I^B, alleles, no A or B antigens were added to cell surface FUT1 is the gene mutation that causes this - Wild-type allele for Drosophila is w^r- Eye color of wild-type fruit fly is red4.6 Lethal Alleles Represent Essential Genes- Ex: Mouse A^Y allele- Ex: Human H allele causing Huntington’s disease- Essential genes are those that are required for survival- One wild-type allele may be sufficient to produce enough of the essential product for survivalo Such a mutation behaves as a recessive lethal allele- Mutations resulting in the synthesis of a nonfunctional protein can often be tolerated in the heterozygoteo Recessive lethal alleles result in homozygous recessive individuals that don’t survive Approx. 1/3 of all genes are essential for survival (8700)- In some cases the allele responsible for a lethal effect when homozygous may also result in a distinctive mutant phenotype when present heterozygously (behaves as a recessive lethal allele but is dominant with respect to the phenotype)- A mutation in mice causes a yellow coat color that varies in the normal agouti (Wild-type) coat phenotypeo Homozygous yellow coats are lethal in mice (Die before birth)o A^Y = yellow fur (dominant to Agouti, A)o A = Wild-type allele, recessive to A^Yo Heterozygous mice have a yellow coat- The allele responsible for lethal effect when itis homozygous can also result in a distinctivemutant phenotype when it is heterozygous- The mouse A^Y an allele exhibits a :o
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