Chromosome Translocations - EuroGentest

12This is only a brief guide to chromosome translocations. Moreinformation can be obtained from your local regional geneticscentre (www.geneticalliance.org.uk/services.htm) and from theseaddresses:Unique- The Rare Chromosome Disorder SupportGroupTelephone: 01883 330766info@rarechromo.orgwww.rarechromo.orgGenetic Alliance UKUnit 4D, Leroy House,436 Essex Rd.,London, N1 3QPTelephone: 0207704 3141Provides information aboutspecific genetic conditions andcontact details of w.geneticalliance.org.ukModified from leaflets produced byGuy‟s and St Thomas‟Hospital, London; and theLondon IDEAS GeneticKnowledge Park, according to theirquality standards.January 2007Chromosome TranslocationsContact a Family209-211 City Rd.,London,EC1V 1JNHelpline 0808 808 3555 orTextphone 0808 808 3556(Freephone for parents andfamilies, 10am-4pm Mon-Fri,4.30pm-7.30pm al Results andChoices (ARC)Tel: 020 7631 0285info@arc-uk.orgwww.arc-uk.orgEuroGentest and OrphanetFree-access websitesproviding information aboutgenetic testing and links tosupport groups across Europe.www.eurogentest.orgwww.orpha.netThis work was supported by EuroGentest, an EU-FP6 supported NoE contractnumber 512148Illustrations by Rebecca J formation for Patients and Families

2Chromosome Translocations11Points to rememberThe following information discusses what chromosometranslocations are, how they are inherited and when they mightcause problems. This information is designed to be usedalongside the discussions you have with your genetic specialist. People who carry a balanced translocation are usuallyhealthy. The only time that a problem may arise is whenthat person tries to have children.What is a chromosome translocation? A translocation is either inherited from a parent or happensaround the time of conception. A translocation cannot be corrected – it is present for life. A translocation is not something that can be “caught” fromother people. Therefore a translocation carrier can still bea blood donor, for example. People often feel guilty about something like a balancedtranslocation which runs in the family. It is important toremember that it is no-one‟s fault and no-one has done anything to cause it to happen.To understand what a chromosome translocation is, it is helpfulto know about genes and chromosomes.What are genes and chromosomes?Our bodies are made up of millions of cells. Most cells contain acomplete set of genes. Genes act like a set of instructions,controlling our growth and how our bodies work. They are alsoresponsible for many of our characteristics, such as our eyecolour, blood type or height. We have thousands of genes. Weeach inherit two copies of most genes, one copy from our motherand one copy from our father. That is why we often have similarcharacteristics to both of them.

10What about other family members?3Picture 1: Genes, chromosomes and DNAIf a translocation is found, that person may wish to discuss thiswith other family members. This gives other family members theopportunity to have a blood test to see if they also carry thetranslocation, if they wish. This might be particularly important tofamily members who already have children, or are likely to havechildren in the future. If they do not carry a translocation thenthey cannot pass it on to their children, but if they do carry atranslocation they too could be offered a test during pregnancy tocheck the baby‟s chromosomes.Some people find it difficult to tell other members of the familyabout the translocation. They may be worried about causinganxiety in the family. In some families, people have lost touchwith relatives and may feel it is difficult to contact them. Geneticspecialists often have a lot of experience with families in thesesituations and may be able to offer you help in discussing thesituation with other family members.Genes are located on small thread -like structures calledchromosomes. Usually we have 46 chromosomes in most cells.One set of 23 chromosomes we inherit from our mother and oneset of 23 chromosomes we inherit from our father. So we havetwo sets of 23 chromosomes, or 23 pairs.

49Picture 2: 23 pairs of chromosomes arrangedaccording to size; chromosome 1 is the largest. Thelast two chromosomes are sex chromosomes.Therefore it is quite possible for a person who carries a balancedtranslocation to have healthy children, and many do. However,the risk that a carrier of a balanced translocation will have a childwith some degree of disability is higher than average, althoughthe severity of the disability depends on the exact type oftranslocation.Pairs number 1 to 22 look the same in males and females.These are called the autosomes. However the 23 rd pair, knownas the sex chromosomes, are different in males and females.There are two sex chromosomes, the „X‟ chromosome and the„Y‟ chromosome. Females have two X chromosomes (XX), whilstmales have an X chromosome and a Y chromosome (XY). Afemale inherits one X chromosome from her mother and one Xchromosome from her father. A male inherits an X chromosomefrom his mother and a Y chromosome from his father. Thepicture above therefore shows the chromosomes of a male asthe last pair of chromosomes are XY.It is important that we have the correct amount of chromosomematerial, as the genes (that instruct the cells in our body) arefound on the chromosomes. Having some part of a chromosomemissing, or having an extra part of a chromosome, can result inlearning difficulties, developmental delay and health problems ina child.Tests for chromosome translocationsGenetic testing is available to find outwhether a person carries a translocation. Asimple blood test is done, and cells fromthe blood are examined in a laboratory tolook at the arrangement of thechromosomes. This is called a karyotypetest. It is also possible to do a test duringpregnancy to find out whether a baby has achromosome translocation. This is calledprenatal diagnosis and is something youmay wish to discuss with the geneticspecialist (more information about thesetests are available in the CVS andamniocentesis leaflets).

85Unbalanced translocationsWhat is a translocation?If either parent carries a balanced translocation, it is possible thattheir child may inherit an unbalanced translocation in whichthere is an extra piece of one chromosome and/or a missingpiece of another chromosome.A translocation means that there is an unusual arrangement ofthe chromosomes. This can happen because:a) a change has arisen during the making of the egg or thesperm or around the time of conceptionb) an altered chromosome arrangement has been inherited fromeither the mother or the fatherFrequently a child can be born with a translocation although bothparents‟ chromosomes are normal. This is called a “ denovo” (from Latin) or new rearrangement. In this case theparents are unlikely to have another child with a translocation.A child who has an unbalanced translocation may have learningdisability, developmental delay and health problems. Theseriousness of the disability depends on exactly which parts ofwhich chromosomes are involved and how much missing orextra chromosome material there is. This is because some partsof the chromosome are more important than other parts.There are two main types of translocations: a RECIPROCALtranslocation and a ROBERTSONIAN translocation.Reciprocal translocationsA reciprocal translocation occurs when two fragments break offfrom two different chromosomes and swap places. This can beseen in Picture 3.Picture 3: How a reciprocal translocation arisesIf a parent has a balanced translocation will he orshe always pass it on?Not necessarily, there are several possibilities for eachpregnancy: The child may inherit entirely normal chromosomes. The child may inherit the same balanced translocation asthe parent. In most cases the child will not have anyproblems as a result of the translocation. The child may inherit an unbalanced translocation, and maybe born with some degree of developmental delay, learningdisability and health problems. The pregnancy ends in miscarriage.Two normalpairs ofchromosomesParts of twochromosomesbreak off.and re-attachto differentchromosomes

67Robertsonian translocationsWhy do translocations happen?A Robertsonian translocation occurs when one chromosomebecomes attached to another. Picture 4 shows a Robertsoniantranslocation involving two chromosomes.Although about 1 person in 500 has a translocation, we still donot really understand why they happen. W e know thatchromosomes seem to break and rejoin quite often during themaking of sperm and eggs or around the time of conception, andit is only sometimes that this leads to problems. These changesoccur without us being able to control them.Picture 4: How a Robertsonian translocation arisesWhen might this lead to problems?In both the examples we have looked at, the chromosomes havebeen rearranged so that no chromosome material has beenlost or gained. This is called a balanced translocation.A person who carries a balanced translocation is not usuallyaffected by it, and is often unaware of having it. The only time itmay become important is when he or she comes to havechildren. This is because the child may inherit what we call anunbalanced translocation.Two pairs ofnormalChromosomes .Robertsonian translocation:a chromosome from one pairhas become attached to achromosome from anotherpair

Picture 2: 23 pairs of chromosomes arranged according to size; chromosome 1 is the largest. The last two chromosomes are sex chromosomes. Pairs number 1 to 22 look the same in males and females. These are called the autosomes. However the 23rd pair, known as the sex chromosomes, are different in males and females.