Leeds Fetal Medicine Unit Website

Genetic information for patients

This page is intended to give an introduction to some of the genetic concepts that patients coming to the Leeds Fetal Medicine centre might come across. It also has information that may prove useful to other referring clinicicians about some of the rarer genetic conditions that they may not come across frequently (content has been kindly provided by Dr. Jenny Brewster and Dr. Ed Johnstone)

Topics covered

Basic structure of human beings - Chromosomes and Genes
Chromosomal abnormalities
Translocations
Mosaicism
Detection of chromosomal abnormalities
Genetic diseases and syndromes

Basic structure of human beings - Chromosomes and Genes

Human beings are made of billions of cells, small semi-autonomous units that have a cell wall and specialised contents. Different sorts of cell types cluster to form organs such as the heart, brain, kidneys etc. Cells are controlled by a nucleus that each of which contains a complete set of all the genetic information that make us what we are. This genetic information made up of DNA is grouped onto genes, of which there are about 30,000 in normal humans. These genes are in turn grouped together onto 23 pairs of chromosomes (46 in total); girls have two X chromosomes (XX) and boys an X and a Y (XY, see picture b. below). As can be seen from the images below chromosomes are numbered largest to smallest with the sex chromosomes (X or Y) at the end.

Chromosomes as see within a nucleus under a microscope (a.) and having been paired up (b.)

a. b.

Chromosomal abnormalities

Chrosomal abnormalities are conditions characterised by abnormal chromosome patterns, number or arrangements. The commonest chromosomal abnormality is Down's syndrome where an individual has an extra copy of one of the smaller chromosomes, chromosome number 21 (see picture below)

Other common chromosomal abnormalities are Turner's syndrome (where an individual has one X chromosome and no Y), Edward's syndrome (Trisomy chromosome number 18) and Patau's syndrome (Trisomy chromosome number 13). There are other rarer types of chromosomal abnormality, though these tend to miscarry earlier in prgnancy.

Information for each of the above conditions is provided below

Translocations

Chromosomal abnormalities in offspring can also result from balanced translocation in normal adults. For information on translocations (including Robertsonian translocations) click here.

Mosaicism

Mosaicism is a complex concept to understand, that many doctor struggle with, if you are a patient with questions regarding this topic it may be more appropriate to discuss these with us at the Fetal Medicine Unit rather than trying to understand them on your own.

Mosaicism arises from an error in mitosis (cell division) that occurs any time after conception and results in an individual having more than one cell line (types of cell with the same number of chromosomes). This results in some cells having the correct amount of genetic material whereas others will have either an abnormal amount or a defective gene. This can occur in all cells (the somatic line) or can be confined to the germ cell lines (in the gonads (= testes or ovaries)). When confined to the gonads it can produce some unusual and unexpected lines of inheritance.

Somatic mosaicism

The effect of mosaicism is dependent on the percentage of affected cells and where they are. The finding of trisomy 21 in every cell in a little finger would have little or no impact whereas if all the cells in the brain were affected then one would expect similar neurological effects to full blown Down’s syndrome. As it is impossible to predict the percentage of cells affected it is impossible to predict the phenotype, however as a general rule the phenotype will be milder than seen with the pure condition.

Gonadal mosaicism

In gonadal mosaicism, the genetic mutation is present in a proportion of gonadal cells. This is implicated in families with offspring with dominant conditions such as Duchene muscular dystrophy in whom the parents are phenotypically and genetically normal but have affected children. Germ cell mutations are important when considering implications for recurrence of conditions. For example, in the case of Duchenne muscular dystrophy, approximately 2/3 of cases arises from maternal carriers, 5-10% is due to gonadal mosaicism and 25-30% as a result of new mutations.

Detection of chromosomal abnormalities

Chromosomal abnormalities can be detected by looking at any cell of an individual or baby with a nucleus. In fetal medicine we examine a baby's chromosomes by performing amniocentesis, CVS or fetal blood sampling. All of these procedures cary risks and are therefore only usually performed if the chances of abnormality are thought to be relatively high.

Genetic diseases and syndromes

Chromosomes abnormalities usually involve large amounts of genetic material and many thousands of genes, however chromosomes that look normal under the microscope can still contain abnormalities or mistakes in the genetic code that can have significant consequences to the functioning of the gene involved and as a result can cause genetic diseases or syndromes. There are thousands of known genetic conditions, and many more unknown or uncharacterised syndromes. These can be inherited in a variety of ways, each method of inheritance tends to produce a characteristic pattern of affected individuals in a specific family.

Many genetic conditions follow Mendelian inheritance pathways. The common mendelian pathways are:

Autosomal dominant - these conditions (such as Huntington's chorea) tend to be found in every generation of a particular family

Autosomal recessive - these conditions (such as cystic fibrosis) are relatively common, but may be new to a particular family

X-linked recessive - these conditions (such as haemophilia) tend to be found only in males within a family, but are carried by women

Clicking on the above links will provide more information about each of these types of inheritance, as well as some lists of conditions that have each type of inheritance.

Genetic syndromes result from mistakes in the genetic code that make up the genes at a molecular level. These are too small to be seem by the naked eye (even under a microscope), but can be detected by molecular techniques. However, finding where these mistakes are in the first place can be very difficult and takes year of research for each genetic condition. As a result we do not currently know where the mistakes are for all genetic conditions, but do tend to know where the mistakes are for more common conditions such as Cystic Fibrosis. We can therefore test a baby in the womb for conditions such as Cystic Fibrosis if we obtain cells via CVS or amniocentesis, though this carries a risk of miscarriage. We cannot often provide a definitive diagnosis of genetic syndromes using ultrasound, though if a condition is associated with specific physical abnormalities that we can see on scan, we may be able to judge with high probability whether a child does or does not have said condition.

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