Chromosome Mutations

Variation in Chromosome Number

• Euploidy: having full sets of chromosomes

– Haploid

– Diploid

– Triploid

• Aneuploidy: having anything other than full sets

of chromosomes

– Monosomy

– Trisomy

Variation in Chromosome Number

• Polyploidy: having more than two full sets of

chromosomes

– Triploid (3n)

– Tetraploid (4n)

Gross Chromosome Anomalies

CHROMOSOME

ABERRATIONS

• Normal human

– 2n = 46

– 23 distinct pairs of homologous chromosomes

– Sex chromosomes are heteromorphic

• What happens when things aren’t “normal”?

– Missing or extra chromosomes

– Missing or extra “parts” of chromosomes

– Rearrangement of segments of chromosomes

Variations in Chromosome

Number

• Aneuploidy

– One or more individual chromosomes added or

missing

• Polyploidy (Autopolyploidy)

– Multiple complete sets of chromosomes from

same species

• Allopolyploidy

– Multiples of different genomes

Note Table 6.1

Nondisjunction

• Reason for most aneuploidy

• Failure of chromosomes to separate during

meiosis

– Primary nondisjunction

• Meiosis I

• Homologs fail to separate

– Secondary nondisjunction

• Meiosis II

• Chromatids fail to separate

Nondisjunction

Fig. 6-1

Aneuploidy

• Only human conditions that typically

survive are...

– 2n +/- 1

– Examples:

• Klinefelter syndrome (47, XXY)

• Turner syndrome (45, X)

• Down syndrome (47, 21+)

• Patau syndrome (47, 13+)

• Edwards syndrome (47, 18+)

Down Syndrome

• Trisomy 21 (47, 21+)

Fig. 6-3

Down Syndrome

• Trisomy 21 (47,21+)

– Mental retardation

– Similar physical characteristics

– Very affectionate

• Nondisjunction of maternal gametes

– Incidence increases with age

Down Syndrome

Fig. 6-4

Spontaneous Abortion

• Aneuploidy is associated with reduced

viability:

– 30% of spontaneously aborted fetuses have

some kind of chromosome abnormality

– 90% of fetuses with chromosome abnormalities

are spontaneously aborted

– 15-20% of all pregnancies are spontaneously

aborted

Polyploidy (Autopolyploidy)

• Multiple complete sets of chromosomes

• Causes

– Failure of all chromosomes to segregate during

meiosis (diploid gamete)

– Double fertilization

• Plants

– Most common

– Often results in desirable qualities

• I.e., larger size, larger fruit, more vigorous, seedless

– Maintained in plants that can be propagated

asexually

Polyploidy (Allopolyploidy)

• Hybridization of two

closely related species

• May be sustainable in

nature if...

– Chromosome sets are

non-homologous

– Form balanced

gametes

– Ex., American cotton

Fig. 6-8

Changes in

Chromosome Structure

Chromosome Breakage

• Chromosomes may break and reattach

– Mistakes are often made during reattachment

• Spontaneous or induced

– Chemicals

– Radiation

Aberrations in Chromosome

Structure

• Deletions

– Part of the chromosome is lost

Fig. 6-11

Aberrations in Chromosome

Structure • Deletions

• Duplications

– A segment of a chromosome is duplicated

within the genome

Fig. 6-11

Aberrations in Chromosome Structure

• Deletions

• Duplications

• Inversions

– Part of a chromosome gets turned around

Fig. 6-11

Aberrations in Chromosome Structure

• Deletions

• Duplications

• Inversions

• Translocations

– A segment of one chromosome gets moved to

another chromosome

Fig. 6-11

Deletions

• Terminal deletions

– The end of a chromosome is lost

• Ex., Cri-du-chat syndrome

– Partial monosomy

• Part of chromosome 5 lost (46,5p-)

– Symptoms

• Mental retardation

• Internal anatomic malformations

• Malformed glottis & larynx

Cri-du-chat Syndrome

• 46, 5p-

Fig. 6-11

Deletions

• Intercalary deletions

– More central portion of

a chromosome is lost

– Requires formation of

compensation loop

during synapsis

– Results in homozygous

loss of chromosome

segment

Fig. 6-10

Duplications

• Some are a normal part of the genome

– Gene redundancy

– Ex., rRNA

• E. coli: 0.7% of genome = rDNA

Duplications

• Some are due to unequal crossover events

– Results in duplication and a deletion

Fig. 6-12

Duplications

• Ex., Bar-eye Drosophila

– Duplication of region

of X chromosome

causes reduction in

compound eye facets

Fig. 7-13

Duplications

• May be a mechanism for evolution of new

genes

– Duplication of genes allows original to

maintain its function, while copy can mutate to

form a new gene

Inversions

• Rearrangement of genetic information

Fig. 6-14

Inversions

• Potential problems during meiosis

– Homologs cannot synapse normally

– One has to form an inversion loop

Inversions

• Potential problems during meiosis

– Homologs cannot synapse normally

– One has to form an inversion loop

– Crossover within the loop can result in

abnormal chromosomes

Inversions

• Paracentric inversion

– Centromere not part of inversion

loop

– Results in…

• Normal chromosome

• Dicentric chromosome with

duplication & deletion

• Inversion

• Acentric chromosome with

duplication & deletion

See Fig. 6-15

Inversions

• Pericentric inversion

– Centromere is part of

inversion loop

– Results in…

• Normal chromosome

• 2 chromosomes with

duplication & deletion

• Chromosome with

inversion

See Fig. 6-15

Translocations

• Nonreciprocal translocation

– Part of one chromosome breaks off and attaches

to another chromosome

• Reciprocal translocation

– Exchange of genetic material between two

nonhomologous chromosomes

Reciprocal Translocation

• Causes unusual homolog pairing during

synapsis

– Cross-like pattern

Fig. 6-16

Reciprocal Translocation

• Orientation of homologs can result in

unbalanced gametes

Fig. 6-16

Robertsonian Translocation

• Break on p arm of two non-homologous

acrocentric chromosomes

– Small segments are lost

– Large segments fuse together

Familial Down Syndrome

• Heritable form of

Down syndrome

Fig. 7-17

Fragile Sites

• Regions of chromosomes susceptible to breakage

– May be due to regions of loosely coiled chromatin

– Linked to types of mental retardation and cancer

• Ex., Fragile X syndrome (Martin-Bell Syndrome)

– Most common form of inherited mental retardation

Fig. 7-18

Fragile X

• Due to trinucleotide repeats (CGG) in gene

FMR-1

– “Normally” 6-50 repeats

– Syndrome expressed with >230 repeats

– Repeats may result in the inactivation of the

gene

• FMR-1

– Produces RNA binding protein involved with

transport of mRNA’s

– Prominent in developing brain cells