mutations in chromosome number

1. Mutations Due To Alterations In Chromosome Number
The normal human chromosome complement consists of 46 chromosomes comprising 22
morphologically different pairs of autosomes and one pair of sex chromosomes. Variation in either
chromosome number or structure frequently results in significant mental and/or clinical
abnormalities. Chromosomal syndromes are associated with specific chromosomal abnormalities.
Introduction
With the discovery in 1956 that the correct chromosome number in humans is 46, the new era of
clinical cytogenetics began its rapid growth. During the next few years, several major
chromosomal syndromes with altered numbers of chromosomes were reported. Since then it has
been well established that chromosome abnormalities contribute significantly to genetic disease
resulting in reproductive loss, infertility, stillbirths, congenital anomalies, abnormal sexual
development, mental retardation and pathogenesis of malignancy.
Chromosome numbers can vary in two main ways
A… Euploidy B… Aneuploidy
A. Euploidy
Living organisms have either have n or 2n number of chromosomes. Euploidy is the condition in
which changes in the number of chromosomes in the living cells occur in multiples of odd
numbers. The change in number could occur as a single set (monoploidy) or in many multiples of
the basic set of chromosomes.
A.1…Monoploidy. (1x = 1 set of chromosomes instead of normal 2 sets)
The condition is termed monoploidy if among diploid organisms due to certain reasons
irregularities occurring in chromosomal number result in individual having only a single basic set
of chromosome ( haploid )
A.2…Diploidy : (2x = 2 set of chromosomes instead of normal 1 set)
Diploidy is a condition in which due to certain reasons the chromosomes occur as twice the haploid
number. Diploidy is possible in living organisms which are haploid like the lower group of plants.
Higher living organisms cannot be considered diploid because normally they have twice the basic
number of chromosomes (2n).
A.3… Polyploidy (nx = n set of chromosomes instead of normal 2 sets)
Multiple of the basic set of chromosome e.g. 2n, 3n, 4n. Polyploidy is classified then to two classes.
A.3.1… Autopolyploidy Polyploidy as a result of duplictions in the SAME species.
All chromosomes come from same ancestral diploid species Four homologous copies of each
chromosome Meiotic pairing, can form bivalents, trivalents, quadrivalents, univalent.

2. A.3.2… Allopolyploids Polyploid formed by hybridization BETWEEN species. An
individual that has an additional set of chromosomes derived from another species; these typically
occur after chromosomal doubling.
B… Aneuploidy
Aneuploidy is the presence of an abnormal number of chromosomes in a cell, such as having 45
or 47 chromosomes when 46 is expected. An extra or missing chromosome is a common cause of
genetic disorders, including some human birth defects. Some cancer cells also have abnormal
numbers of chromosomes. Aneuploidy originates during cell division when the chromosomes do
not separate properly between the two cells.
Different species normally have different numbers of chromosomes from one another, and the term
"aneuploidy" refers to the chromosome number being different from the usual number for that
species.
Aneuploidy arise due to the loss / gain of one or two chromosome.
Monosomy (2n-1) = Loss of one chromosome
Nullisomy ( 2n-2) = Loss of two chromosome
Trisomy ( 2n+1) = One additional chromosome
Tetrasomy (2n+2) = 2 Additional homologous chromosome
B.1… Monosomy (2n-1)
Monosomy is a form of aneuploidy with the presence of only one chromosome from a pair. Partial
monosomy occurs when only a portion of the chromosome has one copy, while the rest has two
copies.
Some conditions caused due to monosomy are:
B.1.1… Turner syndrome (45, X)
Women with Turner syndrome typically have one X chromosome instead of the usual two sex
chromosomes. Turner syndrome is the only full monosomy that is seen in humans—all other cases
of full monosomy are lethal and the individual will not survive development.
Frequency The frequency of Turner syndrome is about 1 in 8000 newborn females.
Clinical features In newborns often include webbed neck, low hairline, puffy hands
and feet, wide spaced nipples and cardio-vascular problems. Later in life, these girls are typically
short, sexually immature and infertile.
Slightly more than 50% of Turner syndrome patients have a 45, X karyotype. The remaining
Turner patients have other sex chromosome abnormalities of the X-chromosome involving iso-
chromosomes, short-arm deletions and rings.

3. About 30% of Turner patients are mosaics consisting of 45, X cells plus other cells with two or
more normal X-chromosomes, structurally abnormal X-chromosomes or a Y-chromosome.
Approximately 95–99% of 45, X conceptions fail to survive to term and account for about 18% of
chromosomally abnormal spontaneous abortions. The incidence of 45, X is not associated with
maternal age. The paternal X chromosome is missing in about 75% of 45, X patients.
B.1.2…Cri du chat syndrome
French for "cry of the cat" after the distinctive noise by affected persons' malformed larynx. A
partial monosomy caused by a deletion of the end of the short p (from the word petit, French for
small) arm of chromosome 5
B.1.3…1p36 Deletion Syndrome
A partial monosomy caused by a deletion at the end of the short p arm of chromosome 1
B.2…Nullisomy (2n-2)
Nullisomy is a form of aneuploidy with the absence of paired chromosomes.
B.3…Trisomy ( 2n+1)
Trisomy is a form of aneuploidy with the presence of one extra chromosome. Some conditions are
given below.
B.3.1…Trisomy 9
It is a chromosomal disorder caused by having three copies (trisomy) of chromosome number 9.
Indications. Symptoms vary, but usually result in dysmorphisms in the skull, nervous system,
and developmental delay. Dysmorphisms in the heart, kidneys, and musculoskeletal system may
also occur.
B.3.2…Trisomy 8
It is also known as Warkany syndrome 2. It is a human chromosomal disorder caused by having
three copies (trisomy) of chromosome 8. It can appear with or without mosaicism.]
Properties
Complete trisomy 8 causes severe effects on the developing fetus and can be a cause
of miscarriage. Common findings include retarded psychomotor development, moderate to severe
mental retardation, variable growth patterns which can result in either abnormally short or tall
stature, an expressionless face, and many musculoskeletal, visceral, and eye abnormalities, as well

4. as other anomalies. A deep plantar furrow is considered to be pathognomonic of this condition,
especially when seen in combination with other associated features.
B.3.3…Trisomy 22
It is a chromosomal disorder in which there are three copies of chromosome 22 rather than two. It
is a frequent cause of spontaneous abortion during the first trimester of pregnancy. Progression to
the second trimester and live birth are rare. This disorder is found in individuals with an extra copy
or a variation of chromosome 22 in some or all cells of their body. There are many kinds of
disorders associated with Trisomy 22:
Emanuel Syndrome is named after the genetic contributions made by researcher Dr. Beverly
Emanuel. This condition is assigned to individuals born with an unbalanced 11/22 translocation.
That is, when a fragment of chromosome 11 is moved, or translocated to chromosome 22.
22q11 Deletion Syndrome is a rare condition which occurs in approximately 1 in 4000 births.
This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is
missing or deleted. The effects of this disorder are different in each individual but similarities exist
such as heart defects, immune system problems, a distinctive facial appearance, learning
challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and sometimes psychiatric
issues.
22q11 micro-duplication syndrome is the opposite of the 22q11 deletion syndrome, in this
condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this
deficiency are relatively “normal” as in they don’t possess any major birth defects or major medical
illnesses. This micro-duplication is more common than the deletion; this might be due to the milder
phenotype of the individuals.
Phelan-McDermid Syndrome / 22q13 Deletion Syndrome is a condition caused by the deletion
of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive
delays as well as low muscle tone and sleeping, eating and behavioral issues.
Chromosome Ring 22 is a rare disorder caused by the break and re-join of both ends of
chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on
the amount of genetic information lost during the break/re-join. Major characteristics for this
disorder are mental retardation, muscle weakness and lack of coordination.
Cat Eye Syndrome / Schmid Fraccaro Syndrome is a condition caused by a partial trisomy or
tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of
chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found
three or four times. This syndrome is referred as “Cat Eye” due to the eye appearance of reported
affected individuals who have coloboma of the iris; however, this feature is only seen in about half
of the cases.
Mosaic trisomy 22 is a disorder in which an extra chromosome 22 is found only in some cells of
the body. The severity of each case is determined by the number of cells with this extra copy.

5. Some characteristics of individuals with this condition are cardiac abnormalities, growth
retardation, mental delay, etc.
Complete Trisomy 22 is in contrast with Mosaic trisomy 22; this disorder is characterized by an
extra copy of chromosome 22 which is found in each cell of the body of the affected individual.
These cases are very rare, and most of the affected individuals die before birth or shortly after.
B.3.4…Down syndrome
Down syndrome (DS or DNS) or Down's syndrome, also known as trisomy 21, is a genetic
disorder caused by the presence of all or part of a third copy of chromosome 21. It is typically
associated with physical growth delays, characteristic facial features, and mild to
moderate intellectual disability.
Down syndrome is the most common chromosome abnormality in humans, occurring in about one
per 1000 babies born each year. It is named after John Langdon Down, the British doctor who fully
described the syndrome in 1866. The genetic cause of Down syndrome—an extra copy of
chromosome 21—was identified by French researchers in 1959.
Those with Down syndrome nearly always have physical and intellectual disabilities. As adults,
their mental abilities are typically similar to those of an 8- or 9-year-old. They also typically
have poor immune function and generally reach developmental milestones at a later age. They
have an increased risk of a number of other health problems, including congenital heart
disease, leukemia, thyroid disorders, and mental illness, among others
B.3.5…Edwards syndrome
It is also known as trisomy 18 [T18]) is a chromosomal disorder caused by the presence of all, or
part of, an extra 18th chromosome. This genetic condition almost always results
from nondisjunction during meiosis. It is named after John Hilton Edwards, who first described
the syndrome in 1960. It is the second-most common autosomal trisomy, after Down syndrome
that carries to term.
Edwards syndrome occurs in around one in 6,000 live births, and around 80% of those affected
are female. The majority of fetuses with the syndrome die before birth. The incidence increases as
the mother's age increases. The syndrome has a very low rate of survival, resulting from heart
abnormalities, kidney malformations, and other internal organ disorders.
Trisomy 18 (47, XX, +18) is caused by a meiotic nondisjunction event. With nondisjunction,
a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 18; the gamete
thus has 24 chromosomes. When combined with a normal gamete from the other parent,
the embryo has 47 chromosomes, with three copies of chromosome 18.
B.3.6…Patau syndrome
Patau syndrome is caused by a chromosomal abnormality, in which some or all of the cells of the
body contain extra genetic material from chromosome 13. This can occur either because each cell

6. contains a full extra copy of chromosome 13 (a disorder known as trisomy 13 or trisomy D), or
because each cell contains an extra partial copy of the chromosome.
Full trisomy 13 is caused by nondisjunction of chromosomes during meiosis. The extra genetic
material from chromosome 13 disrupts the normal course of development, causing multiple and
complex organ defects.
Patau syndrome affects somewhere between 1 in 10,000 and 1 in 21,700 live births. Patau's
syndrome is the result of trisomy 13, meaning each cell in the body has three copies of chromosome
13 instead of the usual two.
Trisomy 13 was first observed by Thomas Bartholin in 1657, but the chromosomal nature of the
disease was ascertained by Dr. Klaus Patau in 1960. The disease is named in his honor.
B.3.7…Triple X syndrome
It is also known as triplo-X, trisomy X, XXX syndrome, 47,XXX aneuploidy is a form
of chromosomal variation characterized by the presence of an extra X chromosome in each cell of
a human female. Females with triple X syndrome have three X chromosomes instead of two. The
karyotype reads 47, XXX because the affected individual has 47 chromosomes, as opposed to the
usual 46.
Females with Triple X syndrome are at increased risk of delayed language
development, EEG abnormalities, motor coordination problems and auditory processing disorders,
and scoliosis. They tend to show accelerated growth until puberty. Premature ovarian failure seems
to be more prevalent in these women, but most Triple X females seem to have normal fertility.
They are more likely to struggle with personality and psychological problems, and low self-esteem,
but these respond well to treatment.
B.3.8…Klinefelter syndrome (47, XXY)
It is a form of chromosomal variation characterized by the presence of an extra X chromosome in
each cell of a human male. Males with this syndrome has 2 X chromosomes instead of one. The
karyotype reads 47, XXY because the affected individual has 47 chromosomes, as opposed to the
usual 46.
Klinefelter syndrome has a frequency of about 1 in 1000 newborn males. These individuals are
generally normal in appearance before puberty. After puberty they are frequently ascertained in
infertility clinics or identified by their small testes, breast enlargement and tall stature.
Cytogenetic and molecular data have indicated that 47, XXY is equally likely to result from a
maternal or paternal meiotic non-disjunctional error. Variants of Klinefelter syndrome include
those patients with more than two X-chromosomes, multiple X-chromosome mosaicism and
multiple Y-chromosomes. The presence of additional X-chromosomes (more than two) is
associated with increasing severity of clinical abnormalities including mental retardation, sexual
development and skeletal anomalies.

7. B.3.9…47, XYY syndrome
It is a form of chromosomal variation characterized by the presence of an extra Y chromosome in
each cell of a human male. Males with this syndrome has 2 Y chromosomes instead of one. The
karyotype reads 47, XYY because the affected individual has 47 chromosomes, as opposed to the
usual 46.
Approximately 1 in 1000 newborn males have a 47, XYY karyotype. XYY males have no
discernible clinical features at birth or in infancy. Their mental and physical development is normal
and they are fertile. Although most 47, XYY patients are clinically normal, they tend to be taller
than normal and have an increased tendency for behavioral and learning problems as children and
young adults. Y-chromosome aneuploidy results from paternal meiotic nondisjunction and is not
associated with maternal age.