Structural Abnormalities
Deletions
Translocations
Inversions
Duplications
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Deletions
Small or large
Mutation in one or many genes
Homozygosity or heterozygosity for each
Consequences for gene function
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Deletions
• Loss of chromosomal material
• Large-scale deletions are lethal
• Example: Cri du chat
– Deletion of short arm of chromosome 5
– Affects motor and mental function
– Infant cry resembles a meowing cat
– Specific chromosomal break points are
associated with specific phenotypic
changes
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Cri du chat Syndrome
Variation in phenotype
associated with region
deleted has been observed
Researchers have identified
regions with genes involved
in larynx and nervous
system development
Fig. 6.26
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Cri-du chat syndrome
Deletion in Chrom. 5
Prader-Willi Syndrome
Angelman Syndrome
Deletions in Chromosome 15
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Structural Abnormalities
Deletions
Translocations
Inversions
Duplications
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Translocations
• Exchange of chromosomal segments
between nonhomologous chromosomes
• Two major types
–Reciprocal translocation
–Non-reciprocal translocation
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Types of Translocations
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Burkitt’s lymphoma
Ig- myc
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Reciprocal Translocation: yields normal and defective gamets
ABCDE
KLMN
ABMN
KLCDE
Normal gametes
ABCDE
KLMN
ABMN
KLCDE
Parent
Has complete information
Deletion and
Duplication gametes
ABCDE
ABMN
ABMN
KLMN
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Types of Translocations
– Robertsonian Translocation
• Centromeres from two nonhomologous
chromosomes fuse and chromosomal material
from the short arms is lost
• 5% of Down syndrome cases involve a
Robertsonian translocation between
chromosomes 21 and 14
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Robertsonian Translocation
A translocation between
chromosome 14 and 21 may
produce
• Translocation carrier
• Normal phenotype
• Translocation Down syndrome
• Lethal monosomy 21
• Lethal trisomy 14
• Lethal monosomy 14
Fig. 6.27
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Structural Abnormalities
Deletions
Translocations
Inversions
Duplications
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
•Inversions reorganize DNA sequences
New context
Antennapedia
•Antp protein is made in antennal primordial
cells, where the WT Antp does not express
•Legs grow out in Antp mutant in place of
antenna
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Wild-type head
Antp expressed in head
Antp required for identity of T2 (Wings and legs)
Expression of Antp in head results in legs forming in place
of antennae
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Structural Abnormalities
Deletions
Translocations
Inversions
Duplications
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Evolution of genes/gene families
Hemoglobin family
ß family
gene duplication
divergence
a family
(~ 450 million years ago)
myoglobin
gene duplication
divergence
(~ 700 million years ago)
Primordial gene
Encodes O2 carrier protein
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Other Chromosomal Abnormalities
• Uniparental disomy
– Both copies of a chromosome are
inherited from a single parent
– Due to error in cell division
– Examples
• Females affected with rare X-linked disorders
• Prader-Willi and Angelman syndromes
• Fragile sites
– Over 100 have been identified
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Uniparental Disomy
Fig. 6.29
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning
Fragile Sites
on the Human X Chromosome
Fig. 6.30
Chapter 6 Human Heredity by Michael Cummings ©2006 Brooks/Cole-Thomson Learning