Chromosomal Rearrangement

Question 1

Chromosome variations

Answer 1

• permanent chromosomal changes can be passed on to offspring if they occur in cells that will become gametes
• 2 types:

1. Chromosomal rearrangement
   
   • changes in the structure of individual chromosomes
2. Variation in chromosome numbers
   
   • one or more individual chromosomes are added or deleted

Question 2

Chromosome variation and genetic disorders

Answer 2

-Cri du chat: deleted region of one of the chromosome 5 pair

• Down syndrome: 3 chromosome 21
  
  • trisomy 21

Question 3

Types of rearrangements

Answer 3

1. Duplication: some genes duplicated
2. Deletion: some genes deleted
3. Inversion: genes arranged backward
4. Translocation: genes on 2 different chromosomes switch places

• consequence of repair mechanisms gone wrong after double-strand DNA breaks
  
  • breaks may be caused by ionizing radiation

Question 4

Deletions

Answer 4

• loss of segment from a chromosome
  
  • either internal or terminal
• arise by terminal ends breaking off or internal ends breaking, and rejoining of incorrect ends
• major effect: loss of genetic information
• detection:
  
  • deletion loops can be detected during meiosis (in prophase 1 the normal chromosome must loop out for the homologous chromosomes to align properly)
  • by a variety of molecular methods that detect lower heterozygosity or gene dosage

Question 5

Consequences of deletions

Answer 5

• loss of DNA sequences
• phenotypic effects depend on size and location of deleted sequence
• deletions that span a centromere result in an acentric chromosome with will be lost during cell division
  
  • may be lethal
• allow expression of alleles that are normally recessive
  
  • pseudodominance
• can affect gene dosage
  
  • when a gene is expressed, the functional protein is produced at the correct level or dosage
  • some genes require 2 copies for normal protein production (if one gene deleted a mutant phenotype results - haploinsufficient)

Question 6

Duplications

Answer 6

• repetition of a segment of a chromosome arm
• tandem duplication is the simplest form
• a single gene or cluster of genes can be duplicated
• about 5% of human genome consists of duplications
• originated from unequal crossing over of misaligned chromosomes during meiosis
  
  • causes duplications and deletions

-part of altered chromosome must loop out to align with homologous chromosome (can be detected)

Question 7

Consequences of duplications

Answer 7

• evolutionary consequence: 3 possibilities
  
  1. Both copies remain the same
     
     • redundancy
     • alters gene dosage
  2. One copy becomes inactive
     
     • pseudogene
  3. One copy acquires a new function (neofunctionalization)

-gene dosage: amount of protein synthesized usually proportional to number of gene copies present, so extra genes may lead to more proteins

• neofunctionalization: source of new genes
  
  • creates multigene families

Question 8

Inversions

Answer 8

• 2 breaks on a chromosome followed by reinsertion in the opposite orientation
• pericentric: centromere is inverted (moves places)
• paracentric: doesnt affect centromere
• change in position can alter gene expression
• genes in/near chromatin may not be expressed
• if no crossing over occurs, no DNA lost, gametes viable
• if crossing over occurs outside inverted region, no DNA lost, gametes viable
• if crossing over occurs inside inverted region, DNA may be lost, gametes may not be viable

Question 9

Crossing over within a paracentric inversion

Answer 9

• formation of an inversion loop so that genes match up
• crossing over within inversion loop creates
  
  • dicentric chromatid: bridge breaks as two centromeres pulled apart
  • acentric chromatid is lost
• gametes have reduction in genetic information and are non viable
• reduced recombination frequency
• reduced fertility

Question 10

Crossing over within pericentric inversion

Answer 10

• formation of inversion loop to line up genes
• half of gametes missing genetic information and not viable
• reduced recombination frequency
• reduced fertility

Question 11

Ruff inversion

Answer 11

• Ruff is a European wading sandpiper
• has 3 types of males
  
  1. independent: displays in leks to attract females
  2. Faeder: mimic females, sneak copulations
  3. Satellite: look like a drabber version of independent
• faeder and satellite have a 4.5Mb chromosomal inversion that arose 3.8 million years ago
• faeders came first
  
  • a rare crossover event restored some of the independent version of the chromosome to the faeder, creating the satellite version
• the inversion is lethal in the homozygous condition

Question 12

Translocation

Answer 12

• Exchange of segments between non-homologous chromosomes, or to a different region on the same chromosome
• can be reciprocal (two-way) or non-reciprocal (one-way)
• if no genetic material is lost, considered a balance translocation
• translocations can alter expression of genes
• eg. Philadelphia chromosome
  
  • fused BRC-ABL gene
  • 5’ section of BCR fused with most of ABL
  • protein produced is a fusion that functions improperly
  • causes chronic myelogenous leukemia (CML) a rare form of cancer that affects certain types of white blood cells