What are chromosomes? What happens to our chromosomes during reproduction? How does a fertilized egg grow into a baby? How does trisomy arise? What is mosaicism? How does mosaicism occur? How is chromosomal mosaicism diagnosed? How does chromosomal mosaicism affect the health of a developing baby or grown adult? What is chromosome testing (karyotyping)? Cytogenetics – chromosome test (karyotype) * How long does the test take? * What if my prenatal test takes longer than 2 weeks? * What if the test is abnormal? * What if I am worried about how my test is going? * Is the result always correct? * What if the test fails and there is no result? FastDNA™ * How is the test done? * How long does the FastDNA test take? * If my result is not abnormal, does that mean my baby has normal chromosomes? * Is the result always correct? * What if the test is abnormal? * Do I still need to have routine chromosome analysis as well as FastDNA? * What if the test fails? * What is the advantage of the FastDNA test? Biochemistry * When can the first trimester blood test be done? * Where can I have blood taken? * What does it mean if I get a high-risk result? * What does it mean if I get a low-risk result? Molecular aneuploidy screening: miscarriages * How long does the test take? * What if the test is abnormal? * What if I'm worried how the test is going? * Is the result always correct? * What if the test fails and there is no result? Molecular DNA testing * What type of samples are required? * Is the sample collection painful? * Is the DNA test 100% accurate? * How long does the testing take? * Can I take the samples myself at home? * Do you check for paternity with the DNA sample? * Will you destroy my DNA once testing is complete? Microarray CGH testing * How long does the test take? * What type of samples are required? * Is the sample collection painful? * What if I am worried about how my test is going? * What if the test is abnormal? * Is the result always correct? * What if the test fails and there is no result? * Will you destroy my DNA once testing is complete? 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. > Chromosomes Chromosome changes How does trisomy arise? What is mosaicism? How does mosaicism occur? 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. This is an illustration of a pair of chromosomes. 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. Show me a picture of all of the chromosomes. What happens to our chromosomes during reproduction? 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. How does a fertilized egg grow into a baby? 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. How is chromosomal mosaicism diagnosed? Chromosomal mosaicism can be diagnosed in three ways: 1. during prenatal diagnosis 2. in an individual's blood sample or skin biopsy 3. 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 life. Prenatal Diagnosis Chorionic villus sampling Amniocentesis Ultrasound Confined mosaicism Uniparental disomy Diagnosis in blood Preimplantation diagnosis How 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 asymetric, 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. What is chromosome testing (karyotyping)? What is chromosome testing Cytogenetics is the study of chromosomes, see chromosomes. Karyotyping is used to describe chromosome analysis which checks for the correct number and structure of chromosomes. Chromosomes can only be seen when a cell is dividing and they can be treated to display a banded pattern, similar to a bar code. We utilise cytogenetics and karyotyping for testing the following: * Prenatal Testing - testing for abnormalities in the fetus of a pregnancy * Blood - testing for chromosomal abnormalities among individuals/people * Miscarriage or Pregnancy tissue - testing for the cause of a miscarriage What is tissue or cell culture? What is tissue or cell culture Human tissues or cells can be encouraged to grow in the laboratory. The cells take time to grow and how quickly this happens depends on the type of tissue being cultured. For example, blood cultures typically take 3 days, prenatal cultures (amniotic fluid and CVS) generally require at least 7-10 days, whereas as miscarriage material can take up to 3 to weeks to grow. Cells in culture Image of human cells in culture visualised down a microscope. Once sufficient cells have been grown the cells are further processed so that chromosomes can be obtained which are then stained to give a ‘banded’ appearance, rather like a ‘barcode’ pattern, see What are chromosomes? Chromosomes can only be seen when a cell is dividing (mitosis), so we must grow or culture a sample in order to obtain sufficient dividing cells for analysis. The stage at which we see the chromosomes is also known as metaphase during mitotis and these cells are sometimes referred to as metaphase cells. Chromosome test results can take on average 10-28 days to be reported depending on the sample type being cultured, Test times. http://www.medgen.ubc.ca/robinsonlab/mosaic/intro/chromosome.htm http://www.sydneygenetics.com/Resources/Whatarechromosomes/tabid/547/Default.aspx