what chromosomes are?

Answer 1

A chromosome is a single large macromolecule of DNA, and is the basic 'unit' of DNA in a cell. It is a very long, continuous piece of DNA (a single DNA molecule), which contains many genes, regulatory elements and other intervening nucleotide sequences. A broader definition of "chromosome" also includes the DNA-bound proteins which serve to package and manage the DNA. The word chromosome comes from the Greek χρώμα (chroma, color) and σώμα (soma, body) due to its capacity to be stained very strongly with vital and supravital dyes.

Chromosomes vary extensively between different organisms. The DNA molecule may be circular or linear, and can contain anything from tens of kilobase pairs to hundreds of megabase pairs. Typically eukaryotic cells have large linear chromosomes and prokaryotic cells smaller circular chromosomes; although there are many exceptions to this rule. Furthermore, cells may contain more than one type of chromosome; for example mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosome in addition to the nuclear chromosomes.

In eukaryotes nuclear chromosomes are packaged by proteins (particularly histones) into chromatin to fit the massive molecules into the nucleus. The structure of chromatin varies through the cell cycle, and is responsible for the compaction of DNA into the classic four-arm structure during mitosis and meiosis. Prokaryotes do not form chromatin, the cells lack proteins required and the circular configuration of the molecule prevents this.

"Chromosome" is a rather loosely defined term. In eukaryotes a small circular DNA molecule may be called either a plasmid or a small chromosome. In viruses, mitochondria, and chloroplasts their DNA molecules are commonly referred to as chromosomes, despite being naked molecules, as they constitute the complete genome of the organism or organelle.

Answer 2

Chromosomes are the larger components of genes which are comprised of strings that form proteins called Desoxyribonucleaic acid. DNA is coprmisied of four types amino acids are formed into strings to form genes. These aminos acids are tyrosine, adenosine, cytosine and guanine. The location of the of these components in the string determines what information the gene contains.

When genes are formed into groups called eukaryotes or individually, karyotypes they trigger a special developmental function such as the formation of proteins that form blood for instance or build proteins that instruct stem cells to form a specifc structure such as a kidney or skin, these structures are called chromosomes.

Answer 3

Chromosomes are the stuff that contains DNA. They help in the process of mitosis (cell division) by splitting and providing each cell with a small percentage of someone's DNA.

Answer 4

yeeeaaa... what Kelly said... that sounds about right...

Answer 5

WHAT ARE CHROMOSOMES?

Introduction
Chromosomes are the packaging for our genetic material, or DNA (deoxyribonucleic acid). DNA carries a specific code that gives instructions to our body on how to grow, develop and function. The instructions are organized into units called genes. Here's a picture of DNA.

There are 46 chromosomes in most cells of the human body. The body is made up of many different cells that are the building blocks for the various tissues and organ systems in our body. If we were able to look inside most cells in a person’s body we would expect to see 46 chromosomes in each cell.
The 46 chromosomes come in 23 matching pairs. We inherit one chromosome in each pair from our mother and one from our father. In the cytogenetics lab, scientists study chromosomes under a microscope. The 46 chromosomes can be organized into 23 pairs according to size, and the patterns of the dark and light bands. This arranged picture of the chromosomes is called a karyotype.

There are 22 pairs of autosomes and 1 pair of sex chromosomes. The sex chromosomes determine whether an individual is male or female. Two X chromosomes make a female and one X and one Y make a male. The word karyotype is also used when describing a person's chromosomal make up. The normal female karyotype is 46, XX. The normal male karyotype is 46, XY
The shorter, upper arm is called the p arm, for petit. The longer arm is called the q arm, because q is the next letter in the alphabet. The central part, joining the two arms, is called the centromere. Each numbered chromosome is unique and can be distinguished from one another by size, the location of the centromere and the pattern of dark and light bands.
Each person inherits one chromosome in each pair from their mother and one from their father. At fertilization or conception, an egg cell (from the mother) and a sperm cell (from the father) fuse to create a fertilized egg. The egg and the sperm each contain half of the total genetic material. When we make our egg or sperm there is an important process of dividing the 46 chromosomes in half, so that the egg contains 22 autosomes and one X chromosome and the sperm contains 22 autosomes and one "sex-determining" chromosome. The sex chromosome in the sperm determines the sex of the baby. If the sperm is carrying an X chromosome the baby will be female. If the sperm is carrying a Y chromosome the baby will be a male. When the 23 chromosomes in the egg fuse with the 23 chromosomes in the sperm the total number in the baby is restored to 46 chromosomes. The fertilized egg starts as a single cell with 46 chromosomes, also called the zygote. All cells in the human body come from that very first cell. In order for the zygote to develop into a baby this single cell must divide. Before cells can divide the chromosomes must replicate themselves. So, in preparation for cell division, each chromosome makes an identical copy of itself. At cell division each chromosome and its identical copy pull apart into two separate daughter cells. Now the daughter cells have the same chromosomes as the original cell. CHANGES TO THE CHROMOSOMES


It is important for us to have the correct number and structure of chromosomes in order to grow and develop "properly". Sometimes people are born with an "altered" number of chromosomes. This extra genetic material or lack of genetic material can cause problems for a developing baby. Aneuploidy is the term used for the gain or loss of a single chromosome, whereas polyploidy refers to the gain of whole sets of chromosomes
In fact, chromosome abnormalities are common. Approximately 15-20% of all recognized pregnancies in the population result in miscarriage, and 50% of those are due to a change in the chromosomes (Robinson et al, 1999).
Chromosome changes can involve: (1) changes to the number of chromosomes (aneuploidy or polyploidy) or, (2) changes to the structure of chromosomes. Changes to the number of chromosomes:
Trisomy

Trisomy is the presence of one extra copy of a chromosome, such that there are 47 chromosomes in total compared to the normal number of 46 chromosomes. Trisomy is common. It has been estimated that approximately 20% of all human conceptions are trisomic (Hassold and Jacobs, 1984). Down syndrome is the most common type of trisomy that babies may be born with. Down syndrome is caused by the presence of an extra chromosome 21. Down syndrome is also called trisomy 21, "tri" for three copies of chromosome 21. The karyotype of Down syndrome is written 47, XX + 21 or 47, XY + 21. 80% of trisomy 21 conceptions result in early miscarriage. Individuals who are born with Down syndrome tend to have facial features that look similar to each other. These individuals will experience mild to severe mental retardation, heart problems and other health concerns throughout their lifetime. Tell me more about Down syndrome.

There are other extra chromosomes that children can be born with. There can be an extra copy of chromosome 13, which is called trisomy 13 or Patau syndrome. Or there can be an extra copy of chromosome 18, which is called trisomy 18 or Edward syndrome. Trisomy 13 and trisomy 18 are very severe chromosome changes and both usually lead to early infant death, often within the first year of life. Most trisomy 13 and 18 conceptions result in early miscarriage.

An extra copy of any of the other autosomes results in early miscarriage.

Changes in the number of sex chromosomes has a less severe effect on development and sometimes individuals with extra sex chromosomes can even be asymptomatic. Examples of the inheritance of an extra sex chromosome include: XXY, XXX or XYY. Klinefelter syndrome is the inheritance of two X chromosomes and one Y chromosome (47, XXY). Klinefelter's is characterized by male development, infertility and potential mild learning problems. Tell me more about Klinefelter syndrome.

How does the extra chromosome get there? (more scientific details)

Monosomy

In general, loss of chromosome material has a more severe effect on the growth of a baby than does the addition of chromosome material. Monosomy is the presence of only one copy of a chromosome when there is usually two copies, such that there are 45 chromosomes in the cell compared to the normal number of 46 chromosomes. Monosomy is more severe than trisomy. Most monosomies probably do not survive to implantation. This explains why monosomy is not often observed even in early pregnancy losses. Other than a few rare reports of monosomy for chromosome 21, only monosomy for the X chromosome is observed in clinically recognized pregnancies. 99% of monosomy X pregnancies end in an early miscarriage.

However, monosomy X can be found in healthy liveborn babies. Turner syndrome is caused by the inheritance of only one copy of the X chromosome. The karyotype of Turner syndrome is written 45, X0. Individuals with Turner syndrome develop as females. Females with Turner syndrome are usually short in stature, have a characteristic webbing of the neck, are infertile and have normal intelligence. (The majority of those that do survive to term are probably ‘mosaics’ i.e. they have a normal cell line in some tissues.)

Show me a picture of changes in the number of chromosomes.

Polyploidy

Triploidy is when there is one complete extra set of chromosomes. An extra copy of each chromosome for a total of 69 chromosomes. Tetraploidy is when there is two extra sets of chromosomes. Two extra copies of chromosomes makes a total of 92 chromosomes. Both of these chromosome changes generally lead to miscarriage, however some triploids can survive to the third trimester of pregnancy.

Marker chromosome
A marker chromosome is an extra piece of a chromosome of unidentified origin. This extra piece of chromosome can also be called an extra structurally abnormal chromosome, a supernumery chromosome or an accessory chromosome, particularly once its origin is known. The effect of this extra chromosome material depends on the chromosome involved and the size of the piece.



Changes to the structure of chromosomes:
There are many different types of structural chromosome changes that can occur. These include deletions, the loss of a piece of a chromosome; duplications, an extra copy of a piece of a chromosome; inversions, a rearrangement of the chromosome material; translocations, an exchange of material between two chromosomes; a ring chromosome, a deletion of the ends of a chromosome followed by the fusion of both ends to form a circular chromosome.

Link to more information on chromosomes.


HOW DOES TRISOMY ARISE?The first step in reproduction is the creation of the reproductive cells or gametes. For women, the gametes are eggs. For men, the gametes are sperm. The egg and the sperm cells contain half of the total chromosome complement, that is, 23 chromosomes instead of 46 chromosomes. This reduction to 23 chromosomes is necessary so that when the egg and the sperm unite at conception, to create a baby, the proper number of chromosomes, 46, is restored in that child. The process of reducing the number of chromosomes from 46 chromosomes to 23 chromosomes in the reproductive cells is called meiosis.
Meiosis is a two-step process of cell division. The first stage is referred to as meiosis I and the second stage is called meiosis II. Normal meiosis is illustrated in the diagram on the left. The diagram is looking at only one chromosome pair in order to simplify the illustration. However, it is important to remember that all 23 chromosome pairs are involved in this process simultaneously. Spermatogenesis is the making of sperm. In spermatogenesis, the result of meiosis is four sperm cells which can develop into mature sperm. Spermatogenesis is an ongoing process throughout life.

The making of eggs or ova is called oogenesis. Oogenesis is different from spermatogenesis. In oogenesis the result of meiosis is one mature egg or ovum and two polar bodies. Polar bodies are smaller cells which are the bi-products of the creation of the mature ovum. During meiosis I the primary oocytes undergoes a very unequal division. The larger cell, which receives most of the cells contents (cytoplasm and organelles), becomes the secondary oocyte, and the other smaller cell becomes the first polar body. In meiosis II, a second unequal cell division occurs in the secondary oocyte. The result is the ovum and the second polar body. The polar bodies die off. The ovum is much larger than a sperm cell and it contains the materials required for development. Human males produce 200,000,000 sperm per day, whereas females produce one egg (usually) each menstrual cycle.

Show me a diagram of the production of sperm and eggs.



Mistakes can happen...
Sometimes there is a mistake in the sorting of the chromosomes during the production of the sperm or the egg. This is called non-disjunction. Non-disjunction can occur during meiosis I or meiosis II. An error in the proper segregation of the chromosomes during both meiosis I and II are pictured below. In meiosis I, the error occurs when the homologous pairs both travel into the same daughter cell. The result is two daughter cells that have two copies of the chromosome (called disomic cells) and two cells that are missing that chromosome (called nullisomic cells). This is shown in diagram a). In meiosis II, the error occurs when the sister chromatids will not separate and thus travel into the same daughter cell. This is shown in diagram b) by the blue sister chromatids.
What causes non-disjunction?
The cause of non-disjunction is unknown. Non-disjunction seems to be a chance event. Nothing that an individual does or doesn't do during their reproductive years can cause these chromosomal changes. We do know that non-disjunction occurs more frequently in the eggs of women as they get older.


So, how does trisomy, three copies of one chromosome in a baby, arise?
At fertilization the egg (23 chromosomes) and the sperm (23 chromosomes) fuse to create a conception, or zygote, which has 46 chromosomes. If a sperm or egg carries an extra copy of one of the chromosomes, due to non-disjunction at meiosis I or meiosis II, there will be a total of 24 chromosomes instead of 23 in the reproductive cell. If this sperm or egg is fertilized by a normal sperm or egg the result will be a total of 47 chromosomes instead of 46. This is illustrated in the diagrams below where an egg carrying 24 chromosomes is fertilized by a sperm with 23 chromosomes.
Monosomy?
Looking at the diagrams above which are illustrating non-disjunction, what happens with the reproductive cells which appear to be empty, that is, the sperm or egg which are lacking a chromosome? If one of these gametes is fertilized by a normal gamete the result is monosomy of the chromosome involved. Monosomy is a deficiency in number of chromosomes and is defined as only one copy of a chromosome that is normally present in two copies. These eggs and sperm, which contain one less chromosome, have 22 chromosomes. When fertilized, the outcome is 45 chromosomes in total. In general, monosomies are less likely to survive when compared to trisomies.


WHAT IS CHROMOSOMAL MOSAICISM?

Introduction
Chromosomal mosaicism is when different cells within an individual, who has developed from a single fertilized egg, have a different chromosomal makeup. Most commonly there will be some cells with a typical number of chromosomes (46 chromosomes) and other cells with an altered number or structure of chromosomes. The most common kind of chromosomal mosaicism found at prenatal diagnosis involves trisomy, where the abnormal cells contain 47 chromosomes. Down syndrome mosaicism is an example of trisomy mosaicism. These individuals have some cells with the typical number of chromosomes (46) and some cells with an extra chromosome 21, for a total of 47 chromosomes. Mosaicism may exist for all kinds of chromosome abnormalities (monosomy, triploidy, structural changes, etc). Although more rare, there may even be mosaicism where both different cell types are abnormal in structure or number, and there are no normal cells involved.

Chromosomes

Chromosome changes

How does trisomy arise?

> What is mosaicism?

How does mosaicism occur?

The cells with abnormal chromosomes may be found in mutiple tissues, or in just one tissue. Consider the example of trisomy 21 mosaicism or Down syndrome mosaicism. In one individual, if we look at a blood sample we may find some cells with 47 chromosomes and some with 46 chromosomes. If we look at a skin sample we may also see some cells with the abnormal number of chromosomes (47) and some with the normal number of chromosomes (46). This is illustrated in diagram a. On the other hand if we look at another individual, it is possible that in one tissue, say skin, we see mostly cells with 46 chromosomes, but in another tissue, say the intestine, we may see mostly cells with an extra chromosome 21, for a total of 47 chromosomes
Changes in the number or structure of chromosomes in different cells of the body can have variable impacts on the proper functioning of the human body. This will be explored in detail throughout this website. In general, as we would expect, individuals who are mosaic for a chromosome change tend to have a less severe form of the condition seen.

Chromosomal mosaicism describes a group of disorders. Any chromosomal change, in number or structure, can be present in a mosaic form. However, trisomy mosaicism is the most common kind ascertained during prenatal diagnosis.



How does trisomy mosaicism occur?
All of the cells in our body come from a single cell, the fertilized egg or zygote. In order for the zygote to develop into a baby, this single cell must grow and divide. Before cells can divide each chromosome must make an identical copy of itself. At cell division each chromosome and its identical copy pull apart into two separate cells. Now the resulting cells, also called daughter cells, have the same chromosome make-up as the original cell. The two new cells will repeat this process. In each cell, the chromosomes will duplicate and divide into two new cells. The result, is 4 cells identical to the first original cell. This process of cell division is called mitosis. Sometimes a mistake can occur when the chromosomes are separating into the two daughter cells. An extra chromosome may travel into the wrong cell or a chromosome may get lost in the separation of the cells. The result would be two daughter cells with different chromosomal make-up.
the green cell represents a cell with an abnormal chromosome make-up. All cells that come from the green cell will share the same chromosome change. We say that all cells originating from that cell are in the same cell line. The baby that develops from this embryo will have some cells in his/her body which have the typical number of chromosomes and some that have the chromosome change.
Trisomy mosaicism can occur in one of two ways:

In an abnormal fertilized egg with 47 chromosomes, one of the cells may lose the extra chromosome at cell division, leaving 46 chromosomes in that cell. All cells that are derived from that cell will have 46 chromosomes. The rest of the cells will have 47 chromosomes.
In a typical zygote with 46 chromosomes, at cell division one of the cells may retain a duplicated copy of one of the chromosomes. This produces a cell with 47 chromosomes. All cells that are derived from that cell also have 47 chromosomes. The rest of the cells will have 46 chromosomes.
In both cases the result is a baby with two different cell lines, one cell line with 46 chromosomes and one with 47 chromosomes
The effect that mosaicism can have on the development and overall health of an individual is extremely variable. We will now delve into the different ways in which chromosomal mosaicism can be diagnosed and what factors are involved in determining the clinical presentation of these conditions.

HOW DOES TRISOMY MOSAICISM OCCUR?
In this section we begin with some background information on the early stages of growth of the zygote.

At fertilization, the egg and the sperm fuse to form a zygote with 46 chromosomes. The single-celled zygote then enters a stage of growth called cleavage. Cleavage produces a rapidly increasing number of cells which get progressively smaller and smaller in size. The zygote divides through a process called mitosis. During mitosis the 46 chromosomes make an identical copy of themselves and each pair of replicated chromosomes pull apart from each other into separate daughter cells.
The purpose of mitosis is to pass on a complete copy of genetic material to each daughter cell. The contents of the daughter cells are identical to the original cell. The diagram on the right illustrates typical mitosis.
In the earliest stages of growth and development the zygote divides successively to create a ball of cells, called the morula. During these early cleavages, each new cell is called a blastomere. Each blastomere contains the identical chromosome content to the precursor cell, usually 46 chromosomes. As the cells multiple, the morula begins to develop an inner hollow space and an inner cell mass. This is the blastocyst stage.


Mistakes can happen...
Sometimes there is a mistake in the separation or segregation of the chromosomes during mitosis. Two sister chromatids may get "stuck together" and travel into the same daughter cell. Or, a malfunction in chromosome sorting may find two identical chromosomes in the same daughter cell. These errors in proper chromosome segregation are called non-disjunction. Previously we discussed non-disjunction during the development of the sperm and the egg, which is called meiotic non-disjunction. Non-disjunction in the zygote is called post-zygotic non-disjunction or mitotic non-disjunction. Anaphase lag is another mechanism where one chromosome simply fails to get incorporated into the nucleus of a daughter cell. Anaphase lag is probably the most common mechanism involved in trisomy mechanism.


Trisomy mosaicism can originate in two ways.
A. Somatic origin

Mitotic non-disjunction in a cell of a fertilized egg with the typical 46 chromosomes, leads to a different cell line with an additional chromosome. Diagram A illustrates a somatic origin of the trisomy. The cell with three copies of the chromosome may continue to grow, however the cell with only one copy of the chromosome is more often severely disadvantaged and usually will not continue to reproduce (Gardner & Sutherland, 1996).

B. Meiotic origin

The other mechanism, which involves loss of the extra chromosome, can occur through a process called anaphase lag in an abnormal fertilized egg with 47 chromosomes. In the process of anaphase lag, the extra chromosome fails to be included in the formation of the new cell and becomes isolated and eventually lost.

This "mistake" in an abnormal trisomic zygote can be seen as a "correction" and is called "trisomic rescue". If trisomic rescue occurs early in post-zygotic divisions and involves the cells destined to become the embryo, then the originally abnormal chromosome content of the fetus may be "rescued". In both situations A and B the timing of non-disjunction greatly impacts the outcome. Two cells lines
If an error occurs in one of the cells after fertilization it is possible to see how a baby might develop with two "lines" of cells with different chromosomal content.
There are two possible scenarios:

the fertilized egg has a normal chromosome complement. The green cell has an abnormal chromosome content and is the result of an error in cell division in one somatic cell. All of the cells multiple. As this conception develops there will be some cells that have 46 chromosomes and some cells that have 47 chromosomes.
the fertilized egg is trisomic with 47 chromosomes. The green cell has the typical number of chromosomes and is the result of trisomic rescue. All of the cells multiple. As this conception develops there will be some cells that have 46 chromosomes and some cells that have 47 chromosomes.
The effect on the health of the developing baby depends on the mosaic "pattern".

The frequency of somatic origin versus meiotic origin of trisomy depends on the chromosome involved. Somatic errors are associated with lower levels of trisomy in the body. In general, meiotic origin is correlated with higher levels of trisomy in the body. The outcome is probably influenced by the viability of trisomic cells in the specific cell lineages (Robinson et al, 1997).

It is important to consider that the baby is derived from only a few cells (1-5 cells) from the 64-celled blastocyst. The majority of cells at the blastocyst stage contributes to the placenta. So, when an error occurs in a cell at the blastocyst stage it is more likely to be a cell that is destined to be part of the placenta than one destined to become the baby.



The mosaic pattern depends on many factors.
1. Number of cells present at the time of the non-disjunction mistake

A very early mistake, as diagramed above, will effect a greater proportion of the cells in the baby. Mosaicism originating from an early mistake, either in the first or second division of the fertilized egg, leads to generalized mosaicism, since most tissues of the baby are affected, often in a "patchy" way.

A mistake which occurs at a later stage, for example at the 64-celled blastocyst stage, will effect a smaller proportion of the cells in the baby. "Later errors" may lead to an abnormal line of cells confined to a certain area or tissue in the developing individual. Theoretically, if the mistake happens just in cells that are destined to become the placenta then the abnormal cells may be confined to the placenta and may not be found in the baby. Or if trisomic rescue occurs in the cells that are destined to become the baby, then the abnormal cells may be confined to the placenta and not found in the baby. This is called confined placental mosaicism. If the mistake happens just in cells that are destined to become the baby, then the abnormal cells will be confined to the baby. This is called confined embryonic mosaicism. Many more cells contribute to the placenta.

It is extremely difficult to diagnose confined mosaicism with certainty because it is impossible to sample all tissues in an individual. We will explore this in greater detail in the clinical diagnosis section.

2. Type of cells involved

The development and health of the affected baby also depends on the type of cells affected by the mistake. The change in number of chromosomes is only important if it affects the function of the tissue(s) involved. If the duplicated chromosome contains genetic instructions that are crucial to the function of that tissue, the effect on the overall function of the tissue might be impaired or, on the other hand, there may even be selection against the affected cells.

3. Survival of trisomic cells

Also important in determining the outcome is the ability of the abnormal cells to survive. The question is, can the cells with the chromosome mistake continue to reproduce? Certain mechanisms involved in cell selection may prevent the abnormal trisomic cells from reproducing, thus minimizing or eliminating the effect of the original non-disjunction error. The specific chromosome involved seems to play a role in determining the survival of the cells. Studies of cell cultures suggest that trisomic cells generally divide less quickly and undergo cell death more commonly than diploid cells.


OVERVIEW OF FACTORS AFFECTING CLINICAL PRESENTATION

> Overview
How is chromosomal mosaicism diagnosed?

Chromosomal mosaicism can be diagnosed in three ways:

during prenatal diagnosis
in an individual's blood sample or skin biopsy
during preimplantation diagnosis

We have organized this section by timing of the diagnosis, which sometimes gives a clue as to how the mosaicism may impact the health of the affected individual. Most of the concerns with chromosomal mosaicism arise when it is identified at prenatal diagnosis. Thus, most comments in this section relate to diagnosis of chromosomal mosaicism either prenatally or in early lifeHow does chromosomal mosaicism affect the health of a developing baby or grown adult?
It seems likely that everyone contains some small number of cells in their body which are chromosomally abnormal.

So, when does chromosomal mosaicism matter?

When chromosomal mosaicism arises during development, pregnancy outcome depends on which tissue, and how much of that tissue is abnormal. In theory, cases with a relatively high proportion of trisomic cells are more likely to be associated with an abnormal outcome than those with a low proportion of trisomic cells. That is, if a majority of the cells are abnormal then human development is likely to be abnormal. If only a tiny fraction of some tissue were involved, the aneuploidy would likely have little effect on growth and development. Perhaps many people carry a tiny and completely unimportant abnormal cell line somewhere in their body. However, a very minor degree of mosaicism could still be important if a crucial tissue carries the abnormal cells. For example, an abnormal chromosome change confined to one part of the brain could theoretically impair neurological function (Gardner & Sutherland, 1996).

As a general principle, an individual with a chromosome abnormality in only some of their tissues is likely to have less severe but qualitatively similar clinical features to that of someone with the non-mosaic form of the same chromosome abnormality. For example mosaic Down syndrome can be associated with a less characteristic facial appearance and milder mental impairment than the those with typical trisomy 21. Some chromosome changes can only exist in a mosaic form, because in a non-mosaic form they are lethal. Sometimes if the distribution of the aneuploid cell line is assymetric, the body shape or appearance may be asymmetric. Generally it is the cells that are aneuploid that are smaller and less developed (Gardner & Sutherland, 1996).



It is worth noting though that chromosomally abnormal cells may also arise with age and contribute to such health problems as the occurrence of cancer. However, most age-related chromosome changes are likely either eliminated due to poor cell growth or have no obvious harmful effect. For example, 45, X0 cells are increasingly common in female blood cells as they age, but appear to have no harmful effect.
CHROMOSOMAL MOSAICISM FOUND IN PRENATAL DIAGNOSIS

Overview
Chromosomal mosaicism, most often involving trisomic cells (47 chromosomes) and typical cells (46 chromosomes), is detected in 1-2% of pregnancies undergoing chorionic villus sampling and in 0.1% of pregnancies undergoing amniocentesis. Chorionic villus sampling is a prenatal diagnosis procedure which involves analysis of the chromosomes in the placenta. Amniocentesis is a prenatal diagnosis procedure which involves chromosome analysis of cells in the amniotic fluid which are cells from the baby. The possibility of mosaicism should be discussed with parents before any prenatal testing procedure is performed.

The clinical outcome of chromosomal mosaicism is strongly dependent on the specific chromosome involved and the number of trisomic cells in both the placenta and the baby. When we see trisomic cells in amniotic fluid this often indicates that there are trisomic cells in the baby too. However, the true level and distribution of trisomic cells cannot be accurately assessed with any prenatal procedure. Therefore, ultrasound is often the best judge of how a baby is developing. What can ultrasound look for?

> Prenatal Diagnosis

Chorionic villus sampling

Amniocentesis

Ultrasound

Confined mosaicism

Uniparental disomy

Diagnosis in blood

Preimplantation diagnosis

What factors which should be considered when trying to predict the outcome of trisomy (or other types of) mosaicism?
1) the chromosome involved
Outcome is more serious for some chromosomes when compared to others. We explore this in detail in the section on "chromosome specific information". This is because trisomy of some chromosomes may not survive at all, unless the trisomic cells are present only in the placenta and not in the baby. A mosaic finding on CVS or amniocentesis involving trisomy 18 or 21 is likely to have far worse implications than a mosaic finding for trisomy 15 or 16. This is because we know that babies with trisomy 15 or 16 cells cannot survive, so if trisomy 15 or 16 is found at prenatal diagnosis it is less likely to indicate the presence of the abnormal trisomic cells in the baby.
Link to chromosome specific information
2) the tissues affected and level of trisomy in those tissues
In theory, cases with a relatively high proportion of trisomic cells are more likely to be associated with an abnormal outcome than those with a low proportion of trisomic cells. Although knowing all of the tissues affected and the level of trisomic cells found in each tissue would be very helpful in predicting the clinical outcome, it is virtually impossible to determine which tissues are affected by the trisomy either prenatally or in a living person. The only way is on autopsy, where each tissue could be analyzed.
3) method of ascertainment
Was chromosomal mosaicism detected on chorionic villus sampling (CVS), amniocentesis, or in a sample of blood? The way that trisomic cells were detected gives some guidance as to what tissues might be affected. For example, the presence of trisomy in CVS shows that the placenta is affected. Generally, the presence of the trisomy in amniotic fluid suggests that at least one fetal tissue may be affected by the trisomy. However, it is possible to have high levels of the trisomy in amniotic fluid with no confirmation of trisomy in blood or skin of the baby at birth. Sometimes in cases which result in fetal death there is no evidence of the trisomy in multiple examined tissues. Likewise it is possible to have trisomy in the baby which is not detected on amniotic fluid sampling. When abnormal cells are discovered in the blood of a living affected individual, that person will show how the presence of the cells effects growth and development.

Link to chorionic villus sampling
Link to amniocentesis
Link to diagnosis in blood
4) ultrasound findings
Because the outcome of trisomy mosaicism can vary widely, ultrasound often offers the best indication as to how the baby is growing and developing. Abnormal cells tend not to grow and develop properly.
Link to ultrasound
5) presence/absence of uniparental disomy
For many chromosomes the effect of uniparental disomy is either unclear or not believed to affect the babies development. However, uniparental disomy for chromosomes 6, 7, 11, 14, and 15 can be of concern.
Link to uniparental disomy
6) number of previous case reports
We often look to previous case reports to try and understand how a mosaic finding may affect an individual's health. It is much more difficult to predict how a chromosomal change will affect a developing individual if there have only been a few reports.

CHORIONIC VILLUS SAMPLING (CVS)

Overview
Chorionic villus sampling (CVS) is an alternative to amniocentesis for prenatal diagnosis. CVS is a prenatal testing procedure offered in certain pregnancies for determination of the karyotype of the fetus. The chorionic villi are part of the placenta. CVS involves removing a small sample of the placenta with a thin needle which is inserted through a woman's abdomen or with a catheter which is inserted through the vagina and cervix. The location of the placenta sometimes dictates which method is used. The procedure is carried out under the guidance of ultrasound. In most pregnancies the chromosomal content detected in the placenta is an accurate representation of the chromosomes in the fetus. CVS is performed at 10-12 weeks gestation.

Prenatal Diagnosis

> Chorionic villus sampling

Amniocentesis

Ultrasound

Confined mosaicism

Uniparental disomy

Diagnosis in blood

Preimplantation diagnosis

There is a 1-2% risk of miscarriage, above the background risk, associated with the procedure. That is, 1/100-1/50 women will lose the pregnancy following this procedure due to complications of the procedure. There is a potential risk of limb reduction defects associated with CVS of approximately 1 in 1000.


The placenta
The placenta is the connection between the mother and her baby. It allows substances to pass from the mother to the baby and from the baby to the mother. It also produces hormones which help support the pregnancy. The fetus and the placenta both develop from the same fertilized egg or zygote. Thus, the chromosome content in the fetus and the placenta are usually the same. In the earliest stages of development, the single-celled zygote undergoes multiple cell divisions. As the cells continue to divide, some start to differentiate, that is they become programmed to develop into a certain cell type. The first cells to differentiate are the trophoblast cells, which are destined to become part of the placenta. The trophoblast cells are involved in implantation of the embryo in the wall of the uterus. In the fully developed placenta, the trophoblast cells are the outer layer of the chorionic villi. Other non-fetal cells become the villus stroma or mesenchymal core. Here's an illustration of the placenta and the baby.

Tell me more about the development of the placenta. (more scientific details)



CVS results
The CVS sample is sent to the laboratory where it can be examined either immediately, or after the cells are cultured and allowed to grow and divide.

Direct analysis is done immediately. This type of analysis examines the trophoblast cells of the placenta. Trophoblast cells are very rapidly dividing cells, which enables them to provide tissue to attach to the uterine wall. This rapid division may bring on a greater vulnerability to mitotic error (Gardner & Sutherland, 1996).
Cultured analysis is done on cultured cells. This type of analysis examines the fibroblast like cells of the villus stroma or mesenchymal core found in the villus structure of the placenta. It is thought that this method more accurately reflect the chromosomes of the fetus. This is because the cells which become the villus stroma is more closely related to the cells which become the embryo, based on early embryonic development.
If it is not specified whether CVS was preformed on ‘direct’ or ‘cultured’ cells it usually means that cultured cells were used.

True chromosomal mosaicism is when two or more cells lines are detected in two or more culture flasks from the same individual. Pseudomosaicism is a term used to describe two cell lines that are found in only one culture flask. Pseudomosaicism is not concerning as it is generally a result of cultural artifact and not representative of a true finding in the baby. It is therefore not normally reported to the patient {Commentary on pseudomosaicism reporting}.



Chromosomal Mosaicism in CVS results
Approximately 1-2% of CVS results cannot be interpreted because of the presence of two cell lines in the placenta with different chromosomal complements (chromosomal mosaicism). When this happens the patient is offered the option of an additional prenatal diagnostic procedure (amniocentesis or fetal blood sampling) in an attempt to clarify the results.

The finding of mosaicism on CVS always requires careful evaluation of the pregnancy as a whole, to try to determine if the abnormal cell line is also present in the fetus or if there is a risk of fetal uniparental disomy (Hahnemann & Vejerslev, 1997).

The result of chromosomal mosaicism on CVS can mean one of four things:

the trisomy cells are only in the placenta and there will be no harmful effect on the development of the baby or the ability of the placenta to function properly. These pregnancies will progress normally.
the trisomy cells are only in placenta and there are no genetic concerns with the development of the baby, however, the presence of the abnormal cells in the placenta impairs its ability to function properly. Some of these babies may be small (IUGR), may be delivered prematurely, and in rare situations the impaired placenta may cause loss of the pregnancy. Link to confined placental mosaicism.
the trisomy cells are only in placental tissue and normal diploid cells are found in the baby. However, a closer look at the chromosomes in the baby show uniparental disomy. Uniparental disomy for certain chromosomes is associated with health concerns. Link to uniparental disomy.
the trisomy cells are both in the placenta and in the baby. Mosaic cells in the baby have a variable effect on growth and development.
It is very important to know that an abnormal CVS result does not mean that there are trisomic cells definitely in the baby. In fact, in most cases the abnormal cells are not suspected to be in the baby or to effect the health of the baby. This result also does not mean that there will definitely be a problem with the ability of the placenta to function.

CVS mosaicism is a very stressful result for expecting parents. When mosaicism is detected on CVS, couples are presented with several options to try to determine if the baby is affected; invasive prenatal options of confirming the mosaicism on amniocentesis or on fetal blood sampling. The other option is to sample fetal skin cells at birth.

AMNIOCENTESIS

Overview
Amniocentesis is the most common test used for prenatal diagnosis of a chromosome problem in the baby. It involves the removing a small amount of amniotic fluid which surrounds the baby in the amniotic sac. Amniocentesis is done after 15 weeks of pregnancy. During the procedure ultrasound is used to locate the baby and the placenta. A thin needle is inserted through the mother’s abdomen into the amniotic sac to remove some of the fluid surrounding the baby. Within the fluid are cells which the baby has shed from its skin and bladder. The sample is taken to the lab and the baby’s cells are separated from the fluid. The cells are grown in the lab and then examined under a microscope. Results on the karyotype of the baby are received in two to three weeks. There is a 0.5-1% risk of miscarriage above the background risk associated with the procedure. That is, 1/200-1/100 women will lose the pregnancy due to complications of the procedure.

Prenatal Diagnosis

Chorionic villus sampling

> Amniocentesis

Ultrasound

Confined mosaicism

Uniparental disomy

Diagnosis in blood

Preimplantation diagnosis

Amniocentesis results
The amniocentesis sample is sent to the laboratory where the cells are cultured (allowed to grow and divide) and then the chromosomes are analyzed. In 12% of amniotic fluid samples that are analyzed more than one cell type is revealed (Chernos, 1994). Usually the mosaicism is not reflective of true fetal mosaicism. The frequency of confirmed chromosome mosaicism detected in amniotic fluid samples is about 0.1% (Bui et al, 1984).

As with CVS, true chromosomal mosaicism is when two or more cells lines are detected in two or more culture flasks from the same individual. Pseudomosaicism is a term used to describe two cell lines that are found in only one culture flask. Pseudomosaicism is not concerning as it is generally a result of cultural artifact and not representative of a true finding in the baby. It is therefore not normally reported to the patient {Commentary on pseudomosaicism reporting}.

Some extra scientific details of mosaicism detection: link.

Amniocentesis following an abnormal CVS result
When a couple is faced with suspected chromosomal mosaicism on CVS, amniocentesis is may be suggested. Whether amniocentesis is performed after the finding of CVS mosaicism depends on the chromosome involved and the type of chromosomal change. In past experience, the pregnancies that most often continue to livebirth without amniocentesis are those involving aneuploidies that have been rarely described in liveborn children, even in a mosaic form, such as trisomy 2, 3 or 7. In contrast trisomy 8, 18 and 21 only rarely continue to term without amniocentesis or fetal blood sampling (Hahnemann & Vejerslev, 1997).
When chromosomal mosaicism is not detected in amniotic fluid, the abnormal cells are thought to be confined to the placenta. Confined placental mosaicism is not of genetic significance to the developing baby. (Goldberg & Wohlferd, 1997) Link to confined placental mosaicism.



What does mosaicism found on amniocentesis mean?
Amniocentesis reveals a mosaic finding in 0.1% of all pregnancies. Generally, the presence of the trisomy in amniotic fluid suggests that at least one fetal tissue may be affected by the trisomy. However, it is possible to have high levels of the trisomy in amniotic fluid with no trisomy cells detected in blood or skin of the baby at birth. There have also been cases in which the amniocentesis result was normal yet fetal mosaicism was present at birth (Phillips et al, 1996).

When mosaicism is detected on amniocentesis fetal blood sampling can be offered, where the expertise is available, to examine cells in fetal blood. If the same abnormal cell line is present in fetal blood, fetal mosaicism would be confirmed. When chromosomal mosaicism is confirmed in the fetus, a couple is presented with a very difficult situation, since fetal abnormality is not a certainty and clinical presentation may be variable. On the other hand, if the fetal blood sampling result is normal the chance of mosaicism in the fetus is greatly reduced. However, abnormal cells may still be present in tissues other than fetal blood. These cases are difficult since fetal mosaicism can never be entirely excluded (Hahnemann & Vejerslev, 1997)

In either case, detailed serial ultrasound examinations may provide some reassurance if there is normal growth and no fetal anomalies detected.