Chromosomal Anomalies
Asst.Prof. Elif Sibel Aslan
• You’ve seen the genes!
• Now you’ll see the chromosomes!
• Have fun!!
Learning Objectives
• Define mutations and polymorphisms.
• Distinguish the three types of DNA mutations: genome, chromosomal,
and gene.
• Diagram a human chromosome and label the centromere, q arm, p arm,
and telomere.
• Illustrate the different types of structural mutations that occur in
chromosomes.
• Illustrate the different types of numerical mutations that occur in
chromosomes.
• A chromosome anomaly, abnormality or aberration
reflects on a typical number of chromosomes or a
structural abnormality in one or more chromosomes.
• A karyotype refers to a full set of chromosomes from
an individual which can be compared to a "normal"
karyotype for the species via genetic testing.
Let’s See some Normal Karyotypes!
Female Male
As you probably know...
•A human normally has 46 chromosomes in each
and every cell
•Every chromosome comes as a double, we
inherit one from each of our parents
Sex chromosomes are the exception
•Sex is determined by the presence or absence of
the Y chromosome
Female 46,XX – Male 46,XY
Chromosome abnormalities
• Polyploidy
• Aneuploidy
• Structural abnormalities
• Usually abnormal
chromosomes cause miscarriage
• In Finland these problems
affect 6 children per thousand newborns
• Our subject today is aneuploidy in humans
and the diseases caused by it
What is a chromosomal mutation?
Basic Concepts Related to Mutation
• Locus
• Allele
• Genetic polymorphism
• Mutation
Aneuploidy
• Individual whole chromosomes
are missing or extra
• In autosomal as well as sex chromosomes
• Trisomy: one whole extra chromosome
present
– In humans only viable trisomies: 21, 13 and 18
• Multiple sex chromosomes
• Monosomy: one whole chromosome missing
– In humans the only viable monosomy is 45,X
Basic Concepts Related to Mutation
Genetic Locus
Locus refers to the position or location of a gene in
the genome. Genetic loci are defined by
chromosomal location, using chromosome bands
(G-band or R-band) or molecular markers
(microsatellites) as a point of reference.
Basic Concepts Related to Mutation
Allele
An allele is the “version” of a gene that is
present at any given locus. Allelic differences are related to
alterations in the nucleotide sequence of a gene.
Basic Concepts Related to Mutation
Genetic Polymorphism
Polymorphism refers to the occurrence of
multiple alleles at a locus, where at least two alleles
appear with a frequency of >1% in the general population.
Mutation: a permanent transmissable
change in the genetic material, usually in a
single gene
Polymorphism: two or more genetically
determined, proportionally represented
phenotypes in the same population
Types of Mutations
• Genomic: abnormal chromosome number
(monosomy, polysomy, aneuploidy)
• Chromosomal: abnormal chromosome
structure
• Gene: DNA sequence changes in specific
genes
• Chromosome anomalies usually occur when
there is an error in cell division following meiosis
or mitosis.
• There are many types of chromosome
anomalies.
• They can be organized into two basic groups,
numerical and structural anomalies.
Numerical
• This is called aneuploidy (an abnormal number of
chromosomes), and occurs when an individual is
missing either a chromosome from a pair
(monosomy) or has more than two chromosomes
of a pair (trisomy, tetrasomy, etc.).
Down Syndrome- Trisomy 21
In humans an example of a condition caused by a numerical
anomaly is Down Syndrome, also known as Trisomy 21 (an
individual with Down Syndrome has three copies of chromosome
21, rather than two).
• Trisomy has been determined to be a function of maternal age.
Symptoms of Down Sendrome
• Heart problems
• Intestinal problems
• Prone to infections
• Typical facial features
• Lower IQ
• Down men cannot
reproduce
• Only half survive to
the age of 40
http://test.cvtcollege.org/Ac_Programs/dms_vascular/images/03C0B067CF5743D3BD133
1B3D1C79C01.jpg
Trisomy 13
http://www.yorku.ca/earmstro/journey/images/pals.jpe
g
• Patau syndrome Symptoms
• Incidence 1:5000 Cleft lip/palate
• If the fetus survives, the Brain malformation
developmental problems Heart problems
are severe, lifespan 1-2 Polydactyly: extra
months at most fingers and toes
Trisomy 18
• Symptoms
– Heart problems
– Internal organ
deformaties
– Mental retardation
– Difficulties eating
• Edward's syndrome and breathing
• Incidence 1:3000 – Small head, back of
the head very
• Average lifespan 1-2 prominent
months, seldom over a
year (5-10 %) – Typical facial features
Abnormalities in the number of sex
chromosomes
• In males
– 47,XXY Klinefelter syndrome (1:600 baby boys)
• No deformities, but testicles don't develop normally,
which affects development in puberty
• Infertility
– 47,XYY, extra Y chromosome (1:1 000 baby boys)
• Prolonges growth, some have learning difficulties or
emotional problems
– 48,XXXY/48,XXYY/49,XXXXXY
• Developmental disabilities, genital deformity
Klinefelter’s Syndrome 47,XXY (1:600 baby boys)
• What type of mutation would cause
a person to have an extra X
chromosome?
– NONDISJUNCTION!!!!
• Occurrence:
– about 1 in 500 males
• Affected persons being relatively
normal.
– Abnormality includes: tall stature,
sterility, enlarged breasts.
Abnormalities in the number of sex
chromosomes
Turner syndrome http://www.healthofchildren.
• In females com/images/gech_0001_00
04_0_img0280.jpg
– 45,X Turner syndrome
(1:5 000 baby girls)
• Short stature, low hairline, cognitive problems, no puberty, infertility, heart
problems
– 47,XXX extra X chromosome (1:600 baby girls)
• No certain symptoms – learning problems may result, puberty may be
delayed
– 48,XXXX/49,XXXXX
• Incomplete puberty, cognitive problems, infertility
An example of monosomy is Turner Syndrome, where the
individual is born with only one sex chromosome, an X.
Aneuploidy-Nondisjunction
• During anaphase, homologous chromosomes separate
• Sometimes, they do not separate, leading to the
formation of a gamete with two copies of one
chromosome
• Called Nondisjunction
• Numerical chromosome anomalies often arise in meiosis,
the process of producing germ cells
• Other reasons: fertilization ”gone wrong”, later mutations
Summary
• Aneuploidy means having too many or too few
chromosomes
• Usually pregnancies with aneuploidic fetuses
don't come to term
• Triploidies 13 and 18 cause severe problems and
early death
• Triploidy 21 is a milder condition in comparison
• Changes in sex chromosome number often cause
so little problems that they are left undetected
Structural Abnormalities
• When the chromosome's structure is altered, this can take
several forms:
• Deletions
• Translocations
• Inversion
• Duplication
• Isochromosom
• Ring chromosom
Deletions!
A portion of the chromosome is missing or deleted.
Onto Deletions!
Cri du Chat
Cry of the Cat individuals
sound like cats crying.
Why?
The larynx of the child is
improperly developed.
Fun Facts About “The Cat”
• The cause of this condition is a deletion of about
half of the short arm of chromosome 5.
• Cri-du-chat babies are severely mentally
retarded, round face, low set ears, heart disease,
and have a small cranium.
• Occurrence:
– 1/1,000,000 live births.
– Karyotype:
46XX or 46 XY with chromosome
#5 upper arm deletion.
Known disorders in humans include:
• Jacobsen syndrome, also called the terminal 11q
deletion disorder.
• Wolf-Hirschhorn syndrome, which is caused by
partial deletion of the short arm of chromosome 4
Translocation!
A portion of one chromosome is transferred to another chromosome. There are two
main types of translocations:
• Reciprocal translocation: Segments from two different chromosomes have been
exchanged.
Reciprocal translocation
• Robertsonian translocation: An entire chromosome has
attached to another at the centromere - in humans these
only occur with chromosomes 13, 14, 15, 21 and 22
Robertsonian translocation
Inversion!
• A condition in which a chromosome segment is
clipped out, turned upside down, and reinserted
back into the chromosome.
• A chromosome inversion can be inherited from
one or both parents, or it may be a mutation that
appears in a child whose family has no history of
chromosome inversion.
pericentric inversion
• An inversion can be 'balanced,' meaning
that it has all the genes that are present in
a normal chromosome; or it can be paracentric inversion
'unbalanced,' meaning that genes have
been deleted (lost) or duplicated.
• A balanced inversion causes no problems.
• An unbalanced inversion is often
associated with problems such as
developmental delay, mental retardation,
and birth defects.
Duplication!
Genes are copied twice !
(during crossover, can get one chromosome with
deletion & one with duplication)
Isochromosomes!
Formed by the mirror image copy of a chromosome
segment including the centromere.
Ring Chromosome!
A portion of a chromosome has broken off and formed a
circle or ring. This can happen with or without loss of
genetic material.
3500000
3000000
2500000
2000000
1500000
1000000
500000
0
1 3 5 7 9 11 13 15 17 19 21 X
Chromosomes
Any Question??