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Our cytogenetic laboratory is an accredited center in Taiwan to
provide karyotyping. Pregnant women who meet the following
criteria can receive 2000NTD subsidy from the government to perform this examination for fetus.
a. Pregnant women who are older than 34 years of age.
b. Pregnant women who have ever born a baby
with chromosome abnormality (such as Down syndrome) or congenital
c. Pregnant women with high risk to have an
d. Pregnant woman or her husband has family
history of inherited diseases.
e. Maternal serum screening showing a risk
>1/270 for Down
Cytogenetics is the study of chromosomes
in number and/or structure. Chromosomes are complex structures located in the cell
nucleus. They are composed of DNA, histone and non-histone proteins, RNA , and polysaccharides. They are basically the "packages" that contain the DNA. Normally chromosomes can't be seen with a light microscope but during cell division they become condensed enough to be easily analyzed. To collect cells with their chromosomes in this condensed state they are exposed to a mitotic inhibitor which blocks formation of the spindle
fiber and arrests cell division at the metaphase stage.
| Under the microscope, chromosomes appear as thin, thread-like structures. They all have a short arm and long arm separated by a primary constriction called the centromere. The short arm is designated as
p and the long arm as q. The centromere is the location of spindle attachment and is an integral part of the chromosome. It is essential for the normal movement and segregation of chromosomes during cell division. Human metaphase chromosomes come in three basic shapes and can be categorized according to the length of the short and long arms and also the centromere location. Metacentric chromosomes have short and long arms of roughly equal length with the centromere in the middle. Submetacentric chromosomes have short and long arms of unequal length with the centromere more towards one end. Acrocentric chromosomes have a centromere very near to one end and have very small short arms. They frequently have secondary constrictions on the short arms that connect very small pieces of DNA, called stalks and satellites, to the centromere. The stalks contain genes which code for ribosomal RNA.
Virtually all routine clinical cytogenetic analyses are done on chromosome preparations that have been treated and stained to produce a banding pattern specific to each chromosome. This allows for the detection of subtle changes in chromosome structure. The most common staining treatment is called G-banding. A variety of other staining techniques are available to help identify specific abnormalities. Once stained metaphase chromosome preparations have been obtained they can be examined under the microscope. Typically 15-20
colonies are scanned and counted with at least 5 cells being fully analyzed.
During a full analysis each chromosome is critically compared band-for-band with it's homolog. It is necessary to examine
many cells in order to detect clinically significant mosaicism.
Following microscopic analysis, either photographic or computerized digital images of the best quality metaphase cells are made.
We are now using automation system to capture, analyze and align
homologous chromosomes. Each chromosome is arranged in pairs according to size and banding pattern into a karyotype.
It allows the
cytogeneticists to even more closely examine each chromosome for structural changes.
According to this careful examination, cytogeneticists can define
and interpret a correct karyotype. In
our laboratory, all the reports are reviewed at least by two
senior cytogeneticists, and are signed by professor Ko. With advanced facilities, experienced
cytogeneticists and conscientious procedure,
all reports can be well interpreted and issued on schedule.
Chorionic Villus Sampling (CVS): 10 mg of Villi
2. Amniocentesis: 15-20 ml of Amniotic
3. Cord blood: 3 ml in heparin
tube (Green Cap)
Place 0.5cm3 tissue block in a
sterilized container with culture medium or normal saline, seal well and send by express delivery at
samples well and send by express delivery to:
Cytogenetic Laboratory, Ko's OBS&GYN
1F., No.10-1, Linsen S. Rd., Zhongzheng District, Taipei City 100, Taiwan
Please call: +886-2-33931030 for assistance.
Normal human somatic cells have 46 chromosomes: 22 pairs, or homologs, of autosomes (chromosomes 1-22) and two sex chromosomes. This is called the diploid number. Females carry two X chromosomes
(46,XX) while males have an X and a Y (46,XY). Germ cells (egg and sperm) have 23 chromosomes: one copy of each autosome plus a single sex chromosome. This is referred to as the haploid number. One chromosome from each autosomal pair plus one sex chromosome is inherited from each parent. Mothers can contribute only an X chromosome to their children while fathers can contribute either an X or a Y.
There are two basic types: numerical and structural. Both types
may occur simultaneously.
Numerical abnormalities involve the loss and/or gain of a whole chromosome or chromosomes and can include both autosomes and sex chromosomes. Generally chromosome loss has a greater effect on an individual than does chromosome gain although
the latter can also have severe consequences. Cells which have lost a chromosome are
monosomy for that chromosome while those with an extra chromosome show trisomy for the chromosome involved. Nearly all
embryos with autosomal monosomies die shortly after conception and only a few trisomy conditions survive to
term. The most common autosomal numerical abnormality is
Down syndrome or trisomy-21. Trisomies for chromosomes 13 and 18 may also survive to birth but are more severely affected than individuals with Down Syndrome.
A condition called
triploidy in which there is an extra copy of every chromosome (69 total), can occasionally survive to birth but usually die in the newborn period.
Another general rule is that loss or gain of an autosome has more severe consequences than loss or gain of a sex chromosome. The most common sex chromosome abnormality is monosomy of the X chromosome (45,X) or
Turner syndrome. Another fairly common example is Klinefelter
syndrome (47,XXY). Although there is substantial variation within each syndrome, affected individuals often lead fairly normal lives.
Occasionally an individual carries a marker
chromosome of unknown origin. The introduction of FISH or SKY techniques has been a valuable tool in the identification of
the origin of marker chromosomes.
Structural abnormalities involve changes in the structure of one or more chromosomes. They can be incredibly complex but for the purposes of this discussion we will focus on
three of the more common types:
Deletions involve loss of material from a chromosome. The effects are typically severe since there is a loss of genetic material.
Inversions occur when there are two breaks within a single chromosome and the broken segment flips 180° (inverts) and reattaches to form a chromosome that is structurally out-of-sequence. There is usually no risk for problems to an individual if the inversion is of familial origin (has been inherited from a parent.)
If the inversion is a de novo (new) mutation, the fetus has a
slightly increased risk of abnormality due possibly to an
interruption of key gene sequences. Although an inversion carrier may be completely normal, they are at a slightly increased risk for producing a chromosomally unbalanced embryo. This is because an inverted chromosome has difficulty pairing with it's normal homolog during meiosis, which can result in gametes containing unbalanced derivative chromosomes if an unequal cross-over event occurs.
Translocations involve exchange of material between two or more chromosomes. If a translocation is reciprocal (balanced) the risk for problems to an individual is similar to that with inversions: usually none if familial and slightly increased if de novo. Problems arise with translocations when gametes from a balanced parent are formed which do not contain both translocation products. When such a gamete combines with a normal gamete from the other parent the result is an unbalanced embryo which is partially monosomic for one chromosome and partially trisomic for the other.
Numerical and structural abnormalities can be further divided into two main categories:
constitutional, those you are born with; and acquired, those that arise as secondary changes to other diseases such as cancer.
Sometimes individuals are found to have both normal and abnormal cell lines. These people are called
mosaics and in the vast majority of these cases the abnormal cell line has a numerical chromosome abnormality. Structural mosaics are extremely rare. The degree to which an individual is clinically affected usually depends on the percentage of abnormal cells. A routine
cytogenetic analysis typically includes the examination of at least 15-20 cells in order to rule out any clinically significant mosaicism.
These are just some of the more common abnormalities encountered by
our laboratory. Because the number of abnormal possibilities is almost infinite,
our trained cytogeneticists can detect and interpret virtually any chromosome abnormality that can occur.
Obstetrics and Gynecology Clinic
1F., No.10, Linsen S. Rd., Zhongzheng District, Taipei City 100, Taiwan
by GenePhile Bioscience Laboratory, Ko's OBS/GYN. All Rights Reserved.