Genetics Lecture 24, 10/29; Large Mutations in Chromosome Structure

Side Note:
Trisomy - 3 copies of one chromosome.
Triploidy - instead of 46 you have 69 chromosomes because you have extra copies of every chromosome

(1:00) Large mutations in Chromosome structure

Deletion: removal of a substantial (as in a whole gene) portion of a chromosome.

• Two Categories of Deletion:
  
• Terminal Deletion: delete from the end of a chromosome
• Intercalary deletion: an internal deletion within the structure of a chromosome
• Cri - du - chat syndrome: a deletion of a small portion of a chromosome results in a substantial effect (baby cries like cat)
• In any deletion, if it is large enough, it will result in death of the organism.

(6:45) Gene Duplication Mutation: a portion of a chromosome copied. Could be anywhere from a single locus to multiple locus, caused by unequal crossover during meiosis.

• Gene redundancy/amplification: deals particularly with essential genes example rRNA gene.
• An organism will have multiple copies of the rRNA gene. rRNA is represented by 0.3 to 0.4% of all genes in an organism. Drosophila has 130 copies of the rRNA gene. If you delete one you have other copies to fill this role. If only a single copy is present of an essential gene, mutation will most likely result in death. In Drosophila, a mutation which decreases the number of copies of the gene still equals poor development and reduced viability. The larger the number of mutated genes the greater the severity.
• (13:25) Gene duplication can lead to phenotypic effects for the cell. Bar eyed phenotype in Drosophila (X-linked dominant mutation)
• heterozygous females and hemizygous males (mutant X chromosome) have one version of the phenotype.
  
• homozygous females have a more severe version of the phenotype.
• in 1930's it was deteremined that all flies have one copy of a particular region of the X chromosome. Your are wild type of you have one copy. The Bar eyed phenotype has two copies of this region. The homozygous females a.k.a. Double bar eyed (the most severe) have 3 copies of this region.
  
• (19:15) Gene duplication could serve as a resovoir for new genes to be produced
• if you have a single copy of an essential gene mutation has a potentially devastating effect.
• if yoy have MULTIPLE copies of a gene you can make one copy and make a new gene with a new function and still have copies of the original gene.
• Evidence that supports this:
• If you compare genes with very different functions there is a relatively high degree of sequence similarity.
• Families of genes. Groups of genes within an organism which are highly similar (80-90% similar) and share similar functions. EX. aminoacyl tRNA synthases: enzymes which link amino acids to tRNA molecules. EACH cell has 20 different forms of this enzyme 1 per unique amino acid.

(26:30) Inversion: a region of chromosome flipped 180 degrees, reordering the genes

• pericentric inversion: the centerosome region is included in the region
• paracentric inversion: the centrosome is not involved
• Two effects of inversion:
• an in version can fuction to prevent synapsis during meiosis
• position effect: being near a region of heterochromatin can change the expression of a gene. If the inversion does this (changes the position relative to heterochromatin) it can be expressed.

(30:50) Translocation: a region of a chromosome moving to an entirely different region of the genome

• major impact is position effect: moving genes closer or farther away from regions of heterochromatin.