Fundamental Genetics

Lecture 7

Chromosome
Mutations
John Donnie A. Ramos, Ph.D.
Dept. of Biological Sciences
College of Science
University of Santo Tomas

Chromosome Mutations

‰ Also called chromosome aberrations

‰ Change in number of chromosomes, deletion
or duplication of genes or segments of
chromosome, or rearrangement of genetic
material
‰ Inherited (can be passed from one generation
to another)
‰ Results to new phenotypic variation or maybe
lethal

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Variation in Chromosome Number

Nondisjunction
‰ Failure of homologous chromosomes to segregate during anaphase of
meiosis
‰ Primary nondisjunction – failure of a homolog to segregation during
anaphase I
‰ Secondary nondisjunction – failure of a homolog to segregate during
anaphase II
‰ Results to aneuploidy

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Monosomy
‰ Loss of one chromosome (2n-1)
‰ Caused by either primary or secondary
nondisjunction
‰ Human Example: Turner syndrome (2n=45, 44+X)
‰ Monosomy involving autosomes in humans is lethal
‰ Drosophila Example: Haplo IV (monosomic at
chromosome no. 4)
‰ Slow development, reduced body size, impaired
viability
‰ Common in plants (maize, tobacco, primrose) – less
viable compare normal plants

Cri-du-Chat Syndrome

‰ Cri-du-Chat syndrome (cry of cat)

‰ Deletion in part of chromosome 5 (46, 5p_)
‰ Gastrointestinal and cardiac complications
‰ Mentally retarded
‰ Abnormal development of glottis and larynx (cry like a cat)
‰ Incidence: 1 in 50,000 births
‰ Different cases have different degrees of truncations

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Trisomy
‰ Gain of chromosome (2n+1)
‰ Caused by either primary or secondary nondisjunction
‰ Affected are viable in humans, animals and plants
‰ Example: Trisomy 21 (Down Syndrome)
‰ Trisomy of chromosome 21 (2n=47, 21+)
‰ 1 in every 800 live births
‰ Flat faces, round heads, protruding and furrowed tongues, short and
broad fingers
‰ Physical, psychomotor, and mental development is retarded
‰ Life expectancy: 50 yrs old
‰ 95 % of cases are nondisjunction in ovum (related to age of female)

Trisomy

‰ Patau Syndrome
‰ (Tisomy 13)
‰ 2n= 47, 13+

‰ Edwards Syndrome
‰ (Trisomy 18)
‰ 2n = 47, 18+

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Polyploids
‰ Presence of more than two sets of chromosomes
‰ Infrequent in many animals species but common in
amphibians, lizards and fishes
‰ Very common in plant species

Same species Different species

(hybridization)

Autopolyploids
‰ Triploid (AAA), tetraploid (AAAA), pentaploid (AAAAA) if A
represents haploid set
‰ Arise as a result of: (for triploids)
‰ Failure of all chromosomes to segragate
‰ Two sperm fertilizing an egg
‰ Experimentally induced (diploid x tetraploid)
‰ Autotetraploids are more likely to occur in nature than
autotriploids (because of genetically unbalanced gametes)
‰ Tetraploids result when chromosomes replicated but sister
chromatids failed to divide
‰ Examples: potatoes, seedless watermelon, commercial bananas,
apples, peanuts, coffee, strawberry (octaploid)

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 Allopolyploids
‰ Hybridization of two closely
related species
‰ Allotretraploid – 4 sets of
chromosomes (Two sets from
species 1 and two sets from
species 2)
‰ Amphidiploid – the resulting
hybrid from2 species
‰ Ex. American cotton (2n=26);
‰ Raphanus brassica (2n=18) =
Raphanus sativus (radish) +
Brassica olaracea (cabbage)
‰ Triticale = rye (high lysine) and
wheat (high protein)

Variation in Chromosome Number

‰ Structural changes in a particular chromosome

‰ Deletions, duplications or rearrangements of
genes
‰ Caused by chromosomal breaks (mutations) –
spontaneous or artificial (due to mutagenic
agents)
‰ Heritable
‰ Can change the phenotype of an organism

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 Deletions
‰ Lost of a gene or a part
of gene
‰ Either terminal or
intercalary deletions
‰ When a chromosome
has intercalary deletion,
its homolog will undergo
compensation loop
during pairing of
homologous
chromosomes.
‰ Example: Cri-du-Chat
Syndrome

Duplications
‰ A gene locus or apiece of chromosome is present more than once
in a genome
‰ Result of unequal crossing-over during meiosis

‰ Can form compensation loop in succeeding homologous pairing

‰ Causes gene redundancy and amplification (ex. Genes coding for
rRNA – E. coli has 5-10 copies but oocyte has 400 copies)
‰ Plays a role in evolution of genes (ex. Trypsin and chymotrypsin
genes; myoglobin and hemoglobin genes; myosin and paramyosin
genes)

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 Duplications
‰ Can cause phenotypic variation
‰ Ex. Bar eye mutation in Drosophila (slit-like eyes)
‰ Identified in 1920s by Alfred Sturtevant and Thomas
Morgan
‰ Duplication in region 16A of X chromosome

Normal Wild-type

Heterozygous

Homozygous
recessive

Double bar

Inversions
‰ Occurs when a region of chromosome is turned 180°
‰ Chromosome part is not lost but rearrangement of genes occur
‰ Two breaks occur

‰ Types:
‰ Paracentric Inversion – centromers is not a part of the
inverted sequence
‰ Pericentric Inversion – centromere is part of the inverted
sequence

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Paracentric Inversion Heterozygotes

‰ Only 1 homolog is inverted

‰ Forms inversion loop
during meiosis
‰ If no crossing-over: results
to 2 normal sequence and
2 inverted sequences
‰ If crossing occurs: results
to 4 different sequence
combinations
‰ Acentric chromosome may
be lost during anaphase

Pericentric Inversion Heterozygotes

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 Translocations
‰ Transfer of chromosome segment to another location (different
chromosome)
‰ Reciprocal translocation – exchange of segments between two
non-homologous chromosomes
‰ Results to partial monosomy or trisomy

Translocations in Humans
‰ Familial Down
Syndrome
‰ 14/21 D/G
‰ Robertsonian
translocation (transfer
of large segment of
chrom. 21 to chrom.
14)

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 Fragile Sites in Humans
‰ Regions in chromosomes susceptible to DNA breakage
‰ Result of short sequence duplications
‰ Examples:
‰ Fragile X Syndrome (Martin-Bell Syndrome)
‰ Presence of Folate-sensitive site on X chromosome
‰ Most common form of mental retardation
‰ Affects 1 in 1250 males and 1 in 1500 females
‰ A dominant trait (but not fully expressed – only 30% and 80% of
females and males with fragile X express the disease, respectively)
‰ Long, narrow faces; enlarge ears; increased testicular size
‰ Caused by FMR-1 gene – (trinucleotide repeats- CGG repeats)
‰ Normal persons = 6-54 repeats; carriers =55-200 repeats; fagile X=
more than 200 repeats)
‰ Undergoes Genetic Anticipation –repeats increase in succeeding
generations
‰ Fragile Sites and Cancer
‰ Lung, stomach, esophagus, colon cancers
‰ Caused by FHIT gene (Fragile histidine triad) located in chromosome 3

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