Benjamin A. Pierce
•GENETICS ESSENTIALS
•Concepts and Connections
• SECOND EDITION
CHAPTER 6
Chromosome Variation
© 2013 W. H. Freeman and Company
THE CASE OF DOWN SYNDROME
• Chromosome 21 and the Down Syndrome Critical Region:
• 5 million base pair region
• 33 genes
• Still not clear
• Indicates complex gene
Interactions at chromosome 21
CHAPTER 6 OUTLINE
• 6.1 Chromosome Mutations Include Rearrangements,
Aneuploids, and Polyploids, 148
• 6.2 Chromosome Rearrangements Alter Chromosome
Structure, 150
• 6.3 Aneuploidy Is an Increase or Decrease in the
Number of Individual Chromosomes, 159
• 6.4 Polyploidy Is the Presence of More Than Two Sets of
Chromosomes, 163
• 6.5 Chromosome Variation Plays an Important Role in
Evolution, 168
6.1 CHROMOSOME MUTATIONS INCLUDE
REARRANGEMENTS, ANEUPLOIDS, AND
POLYPLOIDS
• Chromosome Morphology: (position of the centromere on
the chromosome)
• Metacentric
• Submetacentric
• Acrocentric
• Telocentric
• Karyotype
• Complete set of chromosomes
6.1 Chromosome Mutations Include
Rearrangements, Aneuploids, and Polyploids
• Types of Chromosome Mutations:
• Rearrangements:
• Aneuploidy
• Polyploidy
6.2 CHROMOSOME REARRANGEMENTS
ALTER CHROMOSOME STRUCTURE
• Duplication:
• Tandem
• ABoCDEFEFG
• Displaced
• ABoCDEFGEF
• Or to other chromosome
• Reverse
• ABoCDEFFEG
• What are the consequences?
THE BAR MUTATION AND DUPLICATION IN
DROSOPHILA
• Bar mutation reduces the
number of facets in the eye
• Heterozygous females and
hemizygous males carrying
the mutation have smaller
eyes.
HOW DOES THE DUPLICATION AFFECT
PHENOTYPE?
• Not well understood but gene
dosage is main suspect
• Interactions of many gene
products influence development
• Or novel functions
• Human globin genes
• Segmental duplications on one
chromosome (intrachromosmal) or
on different chromosomes
(interchromosomal)
6.2 CHROMOSOME REARRANGEMENTS
ALTER CHROMOSOME STRUCTURE
• Deletions
• ABoCDEFG becomes ABoCD/G
• Observable on metaphase chromosomes similar to
duplications have looping.
• Consequences:
• Homozygous lethal
• Heterozygous:
• Imbalance
• Pseudodominance
• Haploinsufficient gene
6.2 CHROMOSOME REARRANGEMENTS
ALTER CHROMOSOME STRUCTURE
• Inversions (depending on the involvement of
centromere):
• ABoCDEFG becomes ABoCFEDG (paracentric)
• ABoCDEFG becomes ADCoBEFG (pericentric)
• Consequences (even no genetic material is delted
or gained):
• Gene break
• Position effect
TRANSLOCATION
• Nonreciprocal translocation
• ABoCDEFG and MNoOPQRS leads to ABoCDG and MNoOPEFQRS
• Reciprocal translocation
• ABoCDEFG and MNoOPQRS leads to ABoCDQRG and MNoOPEFS
• Consequences:
• Fused genes leading to fusion
proteins
• Position effect
• Break within a gene
• Robertsonian translocation
6.3 ANEUPLOIDY IS AN INCREASE OR DECREASE IN
THE NUMBER OF INDIVIDUAL CHROMOSOMES
• Causes of Aneuploidy:
• Deletion of centromere during mitosis and meiosis
• Robertsonian translocation
• Nondisjunction during meiosis and mitosis
TYPES OF ANEUPLOIDY
• Nullisomy: loss of both members of a
homologous pair of chromosomes. 2n − 2
• Monosomy: loss of a single chromosome.
2n − 1
• Trisomy: gain of a single chromosome. 2n + 1
• Tetrasomy: gain of two homologous
chromosomes. 2n + 2
• More example
• 2n+1+1 (double trisomy)
• 2n-1-1 (double monosomy)
• 2n+2+2 (double tetrasomy)
6.3 ANEUPLOIDY IS AN INCREASE OR DECREASE IN
THE NUMBER OF INDIVIDUAL CHROMOSOMES
• Effects of Aneuploidy:
• Mostly drastic effects
• Gene dosage
• Aneuploidy in humans:
• Sex-chromosome:
• Turner syndrome. XO
• Klinefelter sydrome. XXY
9.3 ANEUPLOIDY IS AN INCREASE OR DECREASE IN
THE NUMBER OF INDIVIDUAL CHROMOSOMES
• Effects of Aneuploidy:
• In humans:
• Autosomal aneuploids:
• Trisomy 21 – Down sydrome
• Primary Down syndrome,
• 75% random nondisjunction in egg formation.
• Familial Down syndrome,
• Robertsonian translocation between chromosomes 14 and 21.
CARRIERS OF TRANSLOCATIONS: INCREASED
RISK FOR CHILD WITH DOWN SYNDROME
6.3 ANEUPLOIDY IS AN INCREASE OR DECREASE IN
THE NUMBER OF INDIVIDUAL CHROMOSOMES
• Effects of Aneuploidy:
• In humans:
• Autosomal aneuploids:
• Trisomy 18 – Edward syndrome, 1/8000 live births
• Trisomy 13 – Patau syndrome, 1/15,000 live births
• Trisomy 8
1/25,000 ~ 1/50,000 live births
• Why is there a drastic decrease in frequency of these trisomic
syndromes from Chromosome 18 to Chromosome 8?
6.3 ANEUPLOIDY IS AN INCREASE OR DECREASE IN
THE NUMBER OF INDIVIDUAL CHROMOSOMES
• Effects of Aneuploidy:
• In humans:
• Autosomal aneuploids:
• Aneuploidy and maternal age.
• Possible interpretation?
6.4 POLYPLOIDY IS THE PRESENCE OF MORE THAN
TWO SETS OF CHROMOSOMES
• Failure of whole sets of chromosomes to separate
• Tripolids (3n); tertaploids (4n), pentaploidsn (5n)
• Common in plants; less so in animals
• Autopolyploidy:
• From a single species
UNBALANCED CHROMOSOMES AFTER MEIOSIS OF
A TRIPLOID CELL
6.4 Polyploidy is the Presence of More Than
Two Sets of Chromosomes
• Allopolyploidy
• From two species
• Creation of amphidiploid
6.4 Polyploidy is the Presence of More Than
Two Sets of Chromosomes
• The significance of polyploidy:
• Nuclear volume increases-cell volume increases
• Selection of plants with bigger leaves, flowers,
fruits, seeds.
6.5 CHROMOSOME VARIATION PLAYS AN
IMPORTANT ROLE IN EVOLUTION
• New and extra copies of genes give rise to new
functions.
• New and extra sets of genes may give rise to new
species.