CHAPTER 3

• Non-Mendelian Inheritance


  Patterns of inheritance that deviate from Mendelian inheritance
• Several factors must be understood to predict the phenotype of offspring from their genotype
• Mendelian inheritance patterns


  • Involve genes that directly influence the outcome of a trait
  • Obey Mendel's laws
• Most genes in eukaryotic species follow Mendelian pattern of inheritance
• There are many genes that don't follow Mendelian inheritance
• Maternal effect


  Inheritance pattern of certain nuclear genes in which the genotype of the mother directly determines the phenotype of the offspring
• The genotypes of the father and offspring themselves do not affect the phenotype of the offspring in maternal effect
• Maternal effect is due to the accumulation of gene products that the mother provides to her developing eggs
• Maternal effect gene


  • Discovered in the 1920s by A.E. Boycott studying the water snail Limnaea peregra
• Snail coiling


  • Depends on the cleavage pattern of the egg immediately after fertilization
  • Dextral (right-handed) orientation is more common and dominant
  • Sinistral (left-handed) orientation is less common
• Genotype of the mother


  Determines the phenotype of the offspring
• Oogenesis in female animals

  1. Maturing animal oocytes are surrounded by maternal cells that provide them with nutrients

  2. The nurse cells are diploid, whereas the oocyte becomes haploid
• Maternal effect genes encode RNA and proteins that play important roles in the early steps of embryogenesis
• Epigenetic inheritance


  A pattern in which a modification occurs to a nuclear gene or chromosome that alters gene expression, but the expression is not permanently changed over the course of many generations
• Dosage compensation


  A hypothetical genetic regulatory mechanism which equalises the phenotypic expression of genes on the X chromosome, causing equal expression in XY males and XX females

  
• Dosage compensation in mammals

  • Accomplished by the inactivation of one of the X chromosomes in females so that both males and females have only one functional X chromosome per cell

  
• Dosage compensation is not well understood in some species, such as birds and fish

  
• Barr body


  A highly condensed structure in the interphase nuclei of somatic cells in female mammals, identified as an inactivated X chromosome
• X chromosome inactivation (Lyon hypothesis)


  1. One of the two X chromosomes in female mammals is randomly inactivated early in embryonic development

  2. This results in a mosaic pattern of gene expression
• Variegated coat color in mice

  • Due to random X chromosome inactivation
• Variegated coat color


  Patches of black and white fur
• Female mouse


  • Inherited two X chromosomes
  • One from mother with white coat color allele (Xb)
  • One from father with black coat color allele (XB)
• Random X chromosome inactivation

  1. Early embryo - all X chromosomes active

  2. Barr bodies form

  3. White fur allele (Xb) active

  4. Black fur allele (XB) active
• During X chromosome inactivation, the DNA becomes highly compacted and most genes on the inactivated X cannot be expressed
• When the inactivated X is replicated during cell division, both copies remain highly compacted and inactive
• X inactivation is passed along to all future somatic cells
• Variegated coat color is also found in calico cats
• Glucose-6-phosphate dehydrogenase (G-6-PD)


  Enzyme used in sugar metabolism
• 1. 6-PD alleles


  One encodes a "fast" enzyme, another encodes a "slow" enzyme
• Heterozygous adult females produce both types of G-6-PD enzymes, hemizygous males produce either the fast or slow type
• Testing the Lyon hypothesis

  1. Mince tissue to separate cells

  2. Grow cells in liquid medium and plate onto solid medium to form clones

  3. Analyze G-6-PD enzyme in each clone

  
• The experimental results showed that each clone expressed only one type of G-6-PD enzyme, consistent with the Lyon hypothesis
• X inactivation


  • Depends on Xic, Xist, Tsix and Xce regions
  • Xist gene is only expressed on the inactive X chromosome and codes for a long RNA that coats the inactive X
  • Tsix gene is expressed in the opposite direction of Xist and inhibits X inactivation
  • Xce region affects the choice of which X chromosome is inactivated
• Stages of X inactivation

  1. Initiation - one X chromosome targeted for inactivation

  2. Spreading - Xist RNA coats the chosen X and recruits proteins to compact it into a Barr body

  3. Maintenance - the inactivated X is maintained in future cell divisions
• A few genes on the inactivated X chromosome escape the effects of X inactivation
• Genomic imprinting


  Expression of a gene depends on whether it is inherited from the male or female parent
• Barr body


  Replicated and both copies remain compacted
• These genes escape the effects of X inactivation
• Genes that escape X inactivation

  • Xist
  • Pseudoautosomal genes
• Dosage compensation is unnecessary for these genes because they are located on both the X and Y chromosomes