Aetiology: The study of causative factors.
Amniocentesis: One of the techniques for obtaining a sample of fetal cells. It involves the removal by needle of a sample of the fluid around the developing fetus. This contains cells derived from the bladder and lungs after about 14 weeks gestation. These can be persuaded to grow given suitable conditions of nutrition and environment until sufficient dividing cells are present to study the chromosomes (see Mitosis).
Aneuploidy: The loss or gain of a chromosome resulting from non-disjunction, usually in meiosis. It normally refers to whole chromosomes but may be used in relation to extra parts of chromosomes.
Antenatal screening: The examination of pregnant women to assess if they are at higher risk than usual for their age of carrying an affected fetus. In Down syndrome, this may be by maternal serum analysis for the levels of specific fetal proteins or by ultrasound scanning looking specifically for signs such as a large nuchal fold in the fetus. Screening is not diagnosis. Screening can be used for a variety of congenital disorders.
Audit: The process of assessing the efficiency and accuracy of procedures.
Chromosome: Man normally has 23 pairs of chromosomes, comprising 22 pairs of autosomes and a pair of sex chromosomes, XX in the female and XY in the male. Each chromosome carries a specific share of the genome (genetic complement) of the individual.
They are only visible down the light microscope when the cell prepares to divide; between divisions, interphase, the chromosomes can only be seen by the electron microscope as threads of DNA. For simplicity of nomenclature, the chromosomes have been numbered approximately in reducing size (Chromosome 21 is the smallest and the villain in Down syndrome). Number 21 is estimated to have about 300 genes along its arm. Half our chromosomes are derived from mother and half from father. The DNA is reassembled during meiosis so that we receive a mixture of genes from all our grandparents.
Chromosome
anomaly: A broad term including any variation
away from the normal complement of 46 chromosomes in man. It may include
the gain of a whole chromosome (trisomy, aneuploidy), the swapping of parts
between chromosomes (translocation) or the loss or gain of chromosome material.
The vast majority of such changes lead to a gene imbalance and consequent
major or minor congenital anomalies, metabolic changes or neoplastic (cancer
forming) cell types.
Chorionic villus/ CVS: In early pregnancy,the rapidly developing embryo embeds in the wall of the uterus. Part of the embryo differentiates to develop into the placenta. The placenta acts as the anchor for the embryo and is the organ through which oxygen and nutrition pass from the mother to the growing fetus. This transfer is by finger like projections, the chorionic villi, penetrating the highly vascular wall of the uterus. Samples of the tissue can be drawn using a needle under ultrasound visualisation and the rapidly growing cells can provide a diagnosis of the karyotype of the fetus early in pregnancy (12-18 weeks gestation).
Disomic: The presence in a germ cell (spermatozoa or ova) of two chromosomes of the same type.
Double aneuploidy: The presence of two extra chromosomes in a karyotype, often different. Usually leads to miscarriage unless the extra chromosome is an X or Y.
Fetal blood: This tissue is occasionally used for diagnosis, mainly in late pregnancy. Blood is drawn from large vessels on the surface of the placenta near the insertion of the umbilical cord. It allows rapid diagnosis using standard culture methods.
Gametogenesis: This is the process of production of male or female germ cells, spermatozoa or ova (eggs). As each parent is providing half the chromosomes to the new fetus, the number of chromosomes in the germ cell must be reduced to 23. This is achieved in a special form of cell division process called meiosis.
Genetic Centres have been established within the NHS to provide counselling and laboratory services in each health service region. They provide a comprehensive service with clinicians and nurse counsellors available to answer questions and give advice on genetic problems.
Interphase The stages of the cell's life cycle between cell divisions, mitoses. The nucleus is the prominent component of the cell but chromosomes are not visible. It is in this phase that gene expression mainly takes place. Using DNA probes it is now possible to determine (for example) how many chromosomes 21 are present in a nucleus.
Karyotype: An arranged pictorial presentation of the chromosomes of a cell.
Lethal: Causing death in a fetus or newborn.
Meiosis: The cell division process by which germ cells (spermatozoa and ova) are produced. The process involves the reduction in number of the chromosomes from 46 to 23 otherwise on fertilization there would be 96 chromosomes. In order to retain part of the genetic contribution from each grandparent, there is a reshuffling of the chromosome DNA so that the new chromosomes that are formed will contain a blend of genes. The process is in two stages. First, in Meiosis I, there is the pairing and reshuffling of the chromosomal DNA. Then at Meiosis II, there is separation of the two chromosome sets to give a gamete with 23 chromosomes.
The process is different in males and females. In the male, meiosis starts with the onset of puberty. In the female, stage one of meiosis occurs while the fetus is still unborn, with the primordial germ cells laid down in the ovary. The chromosomes reach the stage where they are ready to separate but at this point, meiosis stalls and remain poised in first meiotic division until the child is born and the woman matures. Meiosis does not recommence until that specific ovum is released. This could be any time between puberty and menopause.
Mitosis: The division of somatic (body) cells used in development, growth and repair. Many tissues are composed of 'end' or differentiated cells which have a dedicated function and will no longer divide unless specially stimulated. In the developing embryo all cell types are still capable of division and 'stem cells' are probably capable of dividing many times to produce many different tissues. In mitosis, the cell preparing to divide coils and recoils its threads of DNA until it is in the compact form that we know as chromosomes. Prior to this, the cell has doubled up its DNA so that there will be enough to supply two 'daughter' cells. The chromosomes separate (disjunction) and the two sets of chromosomes are drawn to opposite ends of the cell and form a new interphase nucleus as the DNA uncoils and the two halves separate forming two identical cells.
Miscarriage / spontaneous abortion: The natural process of delivering an abnormal or dead fetus. Perhaps 1 in 5 recognisable pregnancies end as a miscarriage but they can occur late in pregnancy. It is estimated that for DS, between the time of CVS sampling and birth, about 43% of affected fetuses will be naturally miscarried and from the average time for amniocentesis, about 14 weeks, 23% of pregnancies will be lost naturally.
Monozygous: Identical twins derived from one split fertilised egg each therefore having the same genetic make-up. In contrast to dizygous, where both twins have a different genetic make-up being derived from two fertilised eggs.
Mosaicism: Where a person carries two lines of cells with different karyotype or genotype. Chromosomally this can occur in different ways, the ratio normal:abnormal depending on when the error occurred. The most common is for a mitotic non-disjunction leading to two cells one trisomic and the other monosomic, normally lethal to the cell. Depending on the time, site and viability of the surviving cell, this can have a number of effects. If the fetus/child has a low proportion of trisomic cells, there may be no or reduced signs of the syndrome. If the gonad is involved, the resulting adult, while phenotypically normal, may be at higher risk of producing abnormal offspring.
Non-contributive translocation: The term we use to describe a translocation in diagnosed trisomy-21 where the translocation does not involve chromosome 21.
Non-disjunction: The failure of cell division that leads to chromosomes mis-dividing during meiosis or mitosis leading to the loss or gain of a chromosome or chromosomes.
Prenatal diagnosis: Tests used during pregnancy to identify and diagnose an abnormality. In DS this will usually follow a screening procedure which suggests a higher risk but mothers over 35 may be directly referred for diagnosis because of the higher risk in these age groups. Commonly the diagnosis has been based on chromosome analysis for Down syndrome. The advances in DNA analysis will mean an increasing proportion will be initially analysed using a DNA technique such as FISH (Fluorescent In situ hybridisation) or PCR (polymerase chain reaction) related techniques. Normally the result will be confirmed using chromosome studies.
Reciprocal translocation: An exchange of chromosome material between chromosomes. If this is without loss of any genetic material it is called balanced. Carriers of such a translocation will be normal genetically. However, during Meiosis the pairing of the chromosomes may be faulty leading to 'unbalanced' chromosome products and genetic imbalance in any offspring.
Robertsonian translocation: A translocation between two acrocentric chromosomes. The translocation usually involves the loss of the minute short arms and satellites of both chromosomes.
Somatic: Relating to the body rather than the gonads.
Trisomy/ trisomic: The presence of three copies of a chromosome.
