Benjamin A.

Pierce

•GENETICS ESSENTIALS
•Concepts and Connections
• SECOND EDITION

CHAPTER 4
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
 4.1 CHROMOSOME MUTATIONS INCLUDE
REARRANGEMENTS, ANEUPLOIDS, AND POLYPLOIDS

• Chromosome Morphology:
(position of the
centromere on the
chromosome)
• Metacentric
• Submetacentric
• Acrocentric
• Telocentric
 4.1 CHROMOSOME MUTATIONS INCLUDE
REARRANGEMENTS, ANEUPLOIDS, AND POLYPLOIDS

• Karyotype
• Complete set of chromosomes
 Types of Chromosome Mutations:

• Rearrangements:
• Aneuploidy
• Polyploidy
 4.2 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
 THE BAR MUTATION AND DUPLICATION IN
DROSOPHILA
• 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)
 4.2 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
 4.2 CHROMOSOME REARRANGEMENTS
ALTER CHROMOSOME STRUCTURE

• Inversions (depending on the involvement of entromere):

• 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
 TRANSLOCATION

• 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
4.3 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
 4.3 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)
4.3 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
 Effects of Aneuploidy:
• In humans:
• Autosomal aneuploids:
• Trisomy 21 – Down sydrome
• Primary Down syndrome,
• 75% random nondisjunction
in egg formation.
 Effects of Aneuploidy:
• In humans:
• Familial Down syndrome,
• Robertsonian translocation between chromosomes 14 and 21.
CARRIERS OF TRANSLOCATIONS: INCREASED
RISK FOR CHILD WITH DOWN SYNDROME
 4.3 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?
 4.3 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?
 4.4 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
 4.4 Polyploidy is the Presence of More Than
Two Sets of Chromosomes

• Allopolyploidy
• From two species
 4.4 Polyploidy is the Presence of More Than
Two Sets of Chromosomes

• Creation of amphidiploid
4.4 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.
 4.5 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.