is Chromosomal Abnormality?
An error in chromosome number that arose during the
development of an egg or a sperm cell can be termed
as a chromosomonal abnormality. Unlike other cells,
sperm and egg cells have only 23 unpaired chromosomes.
When they unite, pregnancy begins and ultimately results
in the formation of a fertilized egg with 46 chromosomes.
But if an error occurs during cell division, it results
in an embryo with a chromosomal abnormality. A common
type of chromosomal abnormality is called a trisomy.
This means that the individual has 3 copies, instead
of two of a specific chromosome. Down syndrome is the
best cited example for trisomic condition having 3 copies
of chromosome 21.
What is Chromosome?
Chromosomes are tiny string-like structures in cells
of the body that contain the genes. Humans have about
20,000 to 25,000 genes that determine traits like eye
and hair color. They also direct the growth and development
of every part of the body (3).
Each person normally has 23 pairs of chromosomes, or
46 in all. We inherit one chromosome per pair from our
mother and one from our father.
Sometimes, however, a baby can be born with too many
or too few chromosomes, or with one or more chromosomes
that are missing a piece or are rearranged. These errors
in the number or structure of chromosomes can cause
a wide variety of birth defects ranging from mild to
severe. Some chromosomal abnormalities result in miscarriage
What causes Chromosomal abnormalities?
Chromosomal abnormalities usually result from an error
that occurred when an egg or sperm cell was developing.
It is not known why these errors occur. There are two
main types of abnormalities:
1. Numerical abnormalities:
Sometimes the eggs and sperm cells divide incorrectly,
resulting in an egg or sperm cell with too many or too
When this cell with the wrong number of chromosomes
joins with a normal egg or sperm cell, the resulting
embryo has a chromosomal abnormality. A common type
of chromosomal abnormality is called a trisomy. This
means that an individual has three copies, instead of
two, of a specific chromosome. Down syndrome is an example
of a trisomy. Individuals with Down syndrome generally
have three copies of chromosome 21.
In most cases, an embryo with the wrong number of chromosomes
does not survive. In such cases, the pregnant woman
has a miscarriage. This often happens very early in
pregnancy, before a woman may realize she's pregnant.
Up to 75 percent of first trimester miscarriages are
caused by chromosomal abnormalities in the embryo.
2. Structural abnormailities:
When the chromosome's structure is altered. This can
take several forms:
- Deletions: A portion of the chromosome is missing
or deleted. Known disorders include Wolf-Hirschhorn
syndrome, which is caused by partial deletion of the
short arm of chromosome 4; and Jacobsen syndrome,
also called the terminal 11q deletion disorder.
- Duplications: A portion of the chromosome is duplicated,
resulting in extra genetic material. Known disorders
include Charcot-Marie-Tooth disease type 1A which
may be caused by duplication of the gene encoding
peripheral myelin protein 22 (PMP22) on chromosome
- Translocations: When a portion of one chromosome
is transferred to another chromosome. There are two
main types of translocations. In a reciprocal translocation,
segments from two different chromosomes have been
exchanged. In a Robertsonian translocation, an entire
chromosome has attached to another at the centromere;
these only occur with chromosomes 13, 14, 15, 21 and
- Inversions: A portion of the chromosome has broken
off, turned upside down and reattached, therefore
the genetic material is inverted.
- Rings: A portion of a chromosome has broken off
and formed a circle or ring. This can happen with
or without loss of genetic material.
- Isochromosome: Formed by the mirror image copy of
a chromosome segment including the centromere.
Chromosome instability syndromes are a group of disorders
characterized by chromosomal instability and breakage.
They often lead to an increased tendency to develop
certain types of malignancies.
Errors in cell division also can occur soon after fertilization.
This can result in mosaicism, a condition in which an
individual has cells with different genetic makeups.
For example, individuals with the mosaic form of Turner
syndrome are missing an X chromosome in some, but not
all, of their cells. Chromosome anomalies can be inherited
from a parent or be "de novo". This is why
chromosome studies are often performed on parents when
a child is found to have an anomaly.
How are the Chromosomal abnormalities
Chromosomal abnormalities can be diagnosed after birth
using a blood test, or before birth using prenatal tests
(amniocentesis or chorionic villus sampling). Cells
obtained from these tests are grown in the laboratory,
and then their chromosomes are examined under a microscope.
The lab makes a picture (karyotype) of all the person's
chromosomes, arranged in order from largest to smallest.
The karyotype shows the number, size and shape of the
chromosomes and helps experts identify any abnormalities.
Also FISH cytogenetic studies are used for the identification
of chromosomal abnormalities.
What is Kayotyping?
Karyotyping is one of the many techniques that help
study the human genes for several genetic diseases.
Karyotyping comes from the word karyotype. Karyotype
is a complete profile of an individual's chromosomal
set up. Any changes in the arrangement of a karyotype
helps doctors study possible genetic disorders. In simpler
terms, karyotyping is a close study of chromosomes.
What does Kayotyping show?
A karyotype shows the details of the chromosomes. Karyotyping
identifies and helps determine the sex of an unborn
child. When doctors study a human karyotype they look
for some significant features. Here are a few important
Check if the 46 chromosomes are present
Check the presence of the two identical chromosomes
and 2 sex chromosomes
Check if there are any missing or rearranged chromosomes
How is Kayotyping performed?
There are usually no special requirements before performing
the test. It is performed on a sample of blood, bone
marrow, the amniotic fluid or the tissue from the placenta.
Blood is drawn from the body if it requires blood sample.
Amniocentesis is carried out to test amniotic fluid.
A bone marrow test would require a bone marrow biopsy.
The given sample is placed on a tray and allowed to
grow in the confines of a laboratory. The cells from
the growing sample are then stained. The stained sample
is closely examined to study the chromosome arrangement.
How Kayotyping predicts disorders?
A normal human being has 46 chromosomes, 22 autosomes
and two sex chromosomes. When there is a disharmony
between this set up, a genetic disorder occurs. Too
many chromosomes, missing chromosomes or mixed up bits
of chromosomes show the presence of a problem. The state
of the chromosomes helps predict any possible genetic
disorder in an unborn child. Chromosomes carry information
that is passed to the cell. Extra copies of the information,
mixed information or missing information can inform
about any abnormalities or defects.
What makes Kayotyping helpful?
Blood Karyotyping is a very helpful method of studying
chromosomes and predicting genetic disorder. It counts
the number of chromosomes and looks for any structural
changes in chromosomes. It informs if the unborn baby
will suffer from a genetic disorder or not. It is often
used during pre-natal testing and diagnosing possible
genetic diseases. It is extremely helpful for those
who have suffered the loss of a child through a miscarriage.
For couples coping with a miscarriage karyotyping can
mean identifying and correcting problems to give birth
to a healthy child.
What are the Karyotype Options?
Abortus Material (Long term culture)
Amniotic Fluid (Cell Culture)
Ataxia Telengiectasia - Bleomycin assay
Bone Marrow chromosomes
Chorionic Villi samples (Long term culture)
Cord Blood Prenatal- Chromosomes
Falconi’s Anemia (Mitomycin Assay)
Fibroblast culture for other test
Fragile X Syndrome - Thymidine block
Prader Willi syndrome- microdeletion Chm 15
Recurrent Abortions, Husband and Wife
What is FISH cytogenetic study?
Fluorescence in situ hybridisation (FISH) is a powerful
tool for rapid detection of certain chromosome abnormalities
that are otherwise undetectable or difficult to characterise
by conventional cytogenetic methods. It represents a
relatively new type of genetic testing called molecular
cytogenetics, combining the ability to identify a specific
gene or gene region (molecular) with direct visualisation
of the cells and/or chromosomes under the microscope
Applications of FISH for constitutional abnormalities
include detection of origin of marker chromsoomes, delineation
of subtle rearrangements, assaying for deletions and
duplications in cetain syndromes, and chromosomal rearrangements/deletions
on the subtelomeric regions. Examples include: Williams-Beuren
syndrome (7q11.2), DiGeorge/Velocardiofacial/CATCH 22
(22q11.2), Prader Willii and Angelman syndrome (15q11.2),
Smith Magenis (17p11.2), Miller-Diecker/Lissencephaly
(17p13), STS/Steroid sulfatase/Ichthyosis (Xp22.3),
Kallman (Xp22.3), XIST for markers to determine presence
of X inactivation gene in Turner Xq13, Y probes for
sex reversal or other sex chromosome abnormalities (e.g.
Turner with marker), and Charcot-Marie-Tooth disease.
What are the F.I.S.H Study options?
Amniotic Fluid (5 probes 18, 21, 13, X, Y)
Amniotic Fluid culture + F.I.S.H (5 probes)
Chromosome 21/13 only or (X,Y,18)
Chromosome X & Y
What is Microdeletion Syndrome?
A syndrome caused by a chromosomal deletion spanning
several genes that is too small to be detected under
the microscope using conventional cytogenetic methods.
Depending on the size of the deletion, other techniques,
such as FISH or other methods of DNA analysis can sometimes
be employed to identify the deletion
What are the Microdeletion Syndrome
Prader Willli's Syndrome
Miller Decker/Lis gene
Di George Syndrome-Tuple 1 probe
Di George Syndrome-N25 probe
What is Cytogenetic test for Leukemia?
Cytogenetic test for leukemia looks at the chromosomes
in individual cells. It uses a sample taken from a blood
draw or a bone marrow or lymph node biopsy. The sample's
chromosomes are microscopically examined for abnormalities
that indicate damage to the cells' DNA.
What are the Cytogenetic test
options for Leukemia?
Bcr/Abl dual probe (CML)
Translocation 8/ 21 probe (AML)
Transloc. 15 / 17 probe (Ac. P.L)
Breast cancer Her 2 gene amplification
Small cell cancer of Lung - EGFR mutation
Translocation 8/14 (Burkitts, others)
What are the DNA options?
Albinism-OCA 1 Tyrosinase gene sequencing/ Albinism-OCA 2
Alkaptonuria-linkage studies/ Prenatal Diagnosis-linkage
1 Anti Typsin (Z, S & M Mutation)
Aneuploidy screening (21, 18, 13, X, Y, chm)
Angelman Syndrome (methylation test)
Apo E Genotyping
Ataxia Telangiectasia-carrier screening by linkage
Telangiectasia-PND by linkage
Canavan Disease- Asparto asylase (ASPA) gene sequencing
Charcot Marie Tooth disease 1/ HNPP (Del/Dupl. PMP gene)
Congenital Adrenal Hyperplasia-Common deletion
Congenital Adrenal Hyperplasia- 5 mutations
Congenital Adrenal Hyperplasia-deletions by dosage test
Congenital Adrenal Hyperplasia-Prenatal diagnosis-linkage
Congenital Adrenal Hyperplasia-Cyp 21 gene sequencing
Craniosynostosis ( non specific) C749-FGFR 3
Crigler Najjar Syn.- UGT1A1 gene sequencing
Cruozon disease: FGFR 2 mutation (Ser 354 Cys)
Cystic Fibrosis- Diagnosis (Delta 508 mutation)
Cystic Fibrosis- 254 Mutations + Poly T
Cystic Megalencephaly- MLC1 gene sequencing
Cystic Megalencephaly- Prenatal Diagnosis CVS
Deafness Connexin 26 gene-sequencing
DMD deletion testing - 18 exons
DMD 79 exons- deletion/duplication test
DMD-Dosage studies in females
DMD - Prenatal diagnosis + maternal cell contamination
Dystonia (DYT 1 gene- common deletion)
Ectodermal dysplasia X- linked –PND by linkage +MCC
Ectodermal dysplasia X- linked, gene sequencing
Epidermolysis bullosa dystrophia (PND- by linkage)
Factor V Leiden
Familial hypercholesterolemia (linkage, Prenatal)
FGFR 3 gene sequencing (Ach, Hypochond, Thanatophoric dw)
Folate Polymorphism 3' 5 MTHFR ( 677C>T, 1298 A>C)
Fragile X Screen- PCR based
Fragile XA- methylation test
G-6-PD one mutation
Galatosemia gene sequencing (GALT)
Gaucher's disease (4 common mutations)
Gilbert's disease (UGT1A1 Promoter polymorphism)
Glycogen storage 1a gene sequencing
Hallorverden-Spantz disease (PND by linkage)
Hemochromatosis (2 mutations in HFE gene)
Hemophilia A/B, Carrier test
Hemophilia A/B, (Prenatal diagnosis)
Herpes Virus infection (PCR)
Hunter Syndrome - deletions
Hypochondroplasia-common mutation C1620A in FGFR3
Jak 2 mutation
Krabbes disease- common deletion
Leb Hered Optic Atrophy- 3 mutations
Lowe Syndrome - linkage studies/ family
Lowe Syndrome - Prenatal diagnosis-linkage
Maternal Cell Contamination
Marfan Syndrome-linkage studies
Marfan Syndrome - Prenatal diagnosis-linkage studies/ family
MCAD mutation (Medium chain acyl-coA dehyd)
McArdle disease (R49 X mutation, Sequencing)
Merosin deficiency-linkage/ PND
Metaphyseal Dysplasia-COL 10A gene sequencing
Mitochondrial/ LEIGHS or NARP-3 mutations
Mitochondrial 1/ MELAS + MERRF-5 mutations
Mitochondrial package (110, 111)
Mitochondrial genome- deletion/duplication
Mytotonic dystrophy- type 1-19q 13.3
Mytotonic dystrophy- type 2- 3q 21
NCL -infantile (2 mutation)
NCL -infantile (2 mutation)
NCL –Juvenile (Batten Dis) deletion
Neuroblastomatosis (linkage, PND)
Parkinson disease (Gly 19 ser mutation, by sequencing)
Pelizaeus Merzbacher deletion/duplication
Polycystic Kidney dis (Aut. Rec. ARPKD) PND by linkage
Porphyria- Acute intermittent Common Mutation
Porphyria- Sequencing of Porphobilinogen gene
Prader Willi Syndrome-methylation test
Prothrombin gene polymorphism (G20210A)
Restrictive Dermopathy (Specific mutation by sequencing)
Retinoblastoma (Prenatal diagnosis by linkage)
Retinoblastoma gene sequencing
Rett Syndrome MECP2 deletion/ duplication
Rett Syndrome MECP2 -Sequencing
Rh typing - (Rh+ or Rh-)
Rh typing on fetal DNA in maternal blood
Russel Silver Syndrome (UP Disomy)
Spinal Muscular atrophy, diagnosis
Spinal Muscular atrophy-PND
SMA Carrier Screening for deletion
Spinal Muscular atrophy- SMN 1 gene sequencing
Spino- Cerebellar ataxia -One type
Spino- Cerebellar ataxia -Two type
Spino- Cerebellar ataxia -package (1,2,3,6,7,8,12, 17 DRPLA)
Spinal bulbar muscular atrophy (SBMA) CAG repeats
Spondyloepiphyseal dysplasia X-linked gene sequencing
Sry+Amxy gene study (Y chromosome)
Subtelomeic deletions & duplications
Thalassemia-beta (Confirmation of known mutation)
Thalassemia-beta mutation study ( 5 common mutation)
Thalassemia-beta globin gene sequencing
Thalassemia-Prenatal diagnosis-Repeat at GRH
Thanotrophic dwarfism (common mutation)
Thanotrophic dwarfism sequencing
Thrombophilia Profile- 3 genes- MTHFR, Factor v Leiden,Prothrombin
Waardenburg Syndrome Pax 3 gene sequencing
Waardenburg Shah syn- EDN3 gene-3 80A>G
Wilson linkage presymptomatic
Wilson diseases-PND by linkage
Wilson diseases-ATP7B gene sequencing
UGT1A1 * 28 Genotyping
X-linked ichthyosis (Deletion in STS gene)
XMN Polymorphism Gr gene (thalassemia child)
Y-Chromosome deletions (10)
• AB+DR - Additional
person (beyond 2 persons)
• AB+DR - One
• AB+DR - Two
• DQ Alpha -
• DQ Beta -
• DQ Alpha &
beta - Recurrent abortions
M.S. Goodpasture syndrome
• DQ2/DQ8 Celiac
disease High risk genotype
• DR3- , Addison
disease, Derm Nerpc HLA-B5, Behcet's disease
• HLA- Y STR Polymorphism (for two)