Marrying a relative. Is there an increased chance that a child will have genetic problems if its parents are related to each other?
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- Wilfred Waters
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1 Marrying a relative Is there an increased chance that a child will have genetic problems if its parents are related to each other? The simple answer to this question is Yes, there is an increased chance. However, it is important to know that most related couples have healthy children. In some cultures, marrying a relative is traditional. It is considered to have advantages for the people involved, and for their families. It is important to understand that every couple (including those who are not related) has a chance of having a baby with a problem. Some problems are more severe than others, but about 1 in 50 (2%) babies in the UK are born with a serious disability (examples include Down syndrome, spina bifida, and many others). For many of these conditions, the risk of a couple having an affected baby is the same, whether or not the couple are related to each other. However, couples who are related have an increased chance of having a child with certain kinds of inherited, genetic conditions. They are called autosomal recessive genetic conditions. They are caused by the child inheriting a gene with a change or mutation from both parents. To understand this, it is important to know a little about genes and how they can cause disease. What are genes? Our bodies are made up of millions of cells. Each cell contains a complete set of genes. We have thousands of genes. We each inherit two copies of most genes, one copy from our mother and one copy from our father. Genes act like a set of instructions, controlling our growth and how our bodies work. Any alteration in these instructions is called a mutation (or change). Mutations (or changes) can stop a gene from working properly. A mutation (change) in a gene can cause a genetic disorder. Genes are responsible for many of our characteristics, such as our eye colour, blood type or height. Genes are carried on thread-like structures called chromosomes. Each of us has 46 chromosomes in every cell. We inherit our chromosomes from our parents, one set of 23 chromosomes from our mother and one set of 23 chromosomes from our father. So we have two sets of 23 chromosomes, or 23 pairs. One pair of chromosomes are called the sex chromosomes. The other 22 pairs are called autosomes. Changes (mutations) in autosomal genes can cause autosomal genetic disorders. Everyone has two copies (a pair) of every autosomal gene.
2 2 What is autosomal recessive inheritance? An autosomal recessive genetic condition is caused by changes (mutations) in a pair of genes. Both genes must have a change (mutation) for the person to have this disorder. An affected person inherits a copy of the gene with the change (mutation) from each parent. In most cases, the parents of the affected individual are healthy carriers of a single changed copy of the gene. There are thousands of conditions caused by this type of genetic inheritance. Genetic tests are not available for most of these conditions. What does it mean to be a carrier? A carrier of an autosomal recessive deafness gene is a person who has one normal copy of the gene and who has a change (mutation) in the other copy of that gene. The presence of the normal gene usually ensures that the person will not be affected. This is not unusual. It is thought that we are all carriers of a few changed genes. What are the risks for a carrier of having an affected child? Because each person has so many genes, an unrelated couple are not very likely to carry the same gene changes (mutations) as each other. If they do both carry the same changed (mutated) gene, they are at risk of having a child with an autosomal recessive condition. The risk of such a couple having an affected child is 1 in 4, or 25%, for each pregnancy. What are the risks when parents are related? Children inherit their genes from their parents, who inherited them from their own parents. When a couple share some ancestors, as cousins do, it increases the chance that both members of the couple will be carriers of the same gene with a change (mutation). This is because both members of the couple can inherit a copy of the same changed gene from their shared ancestor. This is why couples who are related have an increased chance (when compared with unrelated couples) of having a child with an autosomal recessive condition. For a couple who are first cousins this chance is about 3%, or 1 in 33.
3 Picture 1. How autosomal recessive genes are passed on by parents who are carriers 3 This shape represents a normal working copy of an autosomal recessive gene This shape represents a copy of an autosomal recessive gene with a change (mutation) Both parents have one copy of the autosomal recessive gene with the change (mutation) and one normal copy of the gene. Both parents are carriers of the autosomal recessive condition. not a carrier and does not have the autosomal recessive genetic condition. a carrier of the autosomal recessive genetic condition. a carrier of the autosomal recessive genetic condition. affected by the autosomal recessive genetic condition.
4 4 There are four possible outcomes in pregnancy when both parents are carriers There is a 1 in 4 (25%) chance that the child will be born with the autosomal recessive genetic condition. The child will have inherited two changed genes, one from each parent. There is a 2 in 4 (50%) chance that the child will be a carrier like the parents, but will not have the autosomal recessive genetic condition. The child will have inherited one normal gene and one gene with a change (mutation). There is a 1 in 4 (25%) chance that the child will not inherit the gene with a change (mutation) from either parent. This child will not be a carrier and will not be affected by the autosomal recessive genetic condition. Carrier Testing and Prenatal Diagnosis Carrier testing is available for a very small number of autosomal recessive conditions. This type of testing can establish whether a person carries a particular gene with a change (mutation). Tests are available for some conditions which are particularly common in certain ethnic groups. Examples include cystic fibrosis in white Northern Europeans, thalassaemia in Asian and Mediterranean people, sickle cell anaemia in Afro-Caribbean people and Tay-Sachs disease in people of Eastern European Jewish origin. If both partners are found to be carriers, then it may be possible to offer prenatal diagnosis to find out whether the baby is affected. Prenatal diagnosis involves testing a baby for a genetic disorder during the mother s pregnancy. If you have a family history of a specific medical condition, then it is important to establish whether it is likely to be inherited as an autosomal recessive condition and whether or not carrier testing is possible. This will have been discussed in detail at your genetic clinic appointment.
5 5 Where can I find out more? More information can be obtained from your local regional genetics centre or from these addresses:- The Genetic Interest Group The Genetic Interest Group Unit 4D, Leroy House, 436 Essex Rd., London, N1 3QP Telephone: mail@gig.org.uk Web: Contact a Family Contact a Family City Rd., London, EC1V 1JN Telephone: FAX: Helpline or Textphone (Freephone for parents and families, 10am-4pm, Mon-Fri) info@cafamily.org.uk Web: This edition prepared in July 2005 Ref: 16
6 6 Glossary (difficult words and their meanings): Marrying a relative This glossary is intended only to explain terms used in the information: Marrying a relative. Words shown in bold are defined elsewhere in the glossary. autosomal. Involving the autosomes. autosomal recessive genetic disorders. Disorders caused when a person inherits two copies of an autosomal gene with a change (mutation) in both copies. A person who has only one copy of that autosomal recessive gene with the change (mutation) will be an unaffected carrier. A person who is affected with an autosomal recessive disorder inherits one copy of the disease gene with the change (mutation) from each parent. autosomes. The 44 chromosomes (22 pairs) which are not sex chromosomes. carrier. Someone who has one normal copy of an autosomal recessive gene and who has a change (mutation) in the other copy of that gene. The presence of the normal gene usually ensures that a carrier is not affected by the corresponding autosomal recessive genetic disorder. cell. The human body is made up of millions of cells, which are like building blocks. There are many specialised types of cells. These include skin cells, brain cells, and blood cells. Cells in different parts of the body look different and do different things. Every cell (except for eggs in women and sperm in men) contains all the body s genes. chromosomes. Thread-like structures which can be seen under the microscope and contain the genes. Usually people have 46 chromosomes in every cell. There are two sex chromosomes. The other 22 pairs of chromosomes (numbered 1 to 22) are called autosomes. Twenty-three chromosomes come from the mother, and twenty-three come from the father. One chromosome of each pair comes from each parent. (As an analogy: a chromosome is like a book; a gene is like a story in the book). cystic fibrosis. A genetic disorder caused by having a change (mutation) on both copies of the cystic fibrosis gene. Most children with cystic fibrosis have problems with their lungs and with their digestive system. Down syndrome. A genetic disorder caused by having an extra chromosome 21. Most children with Down syndrome have learning disabilities and they share a typical facial appearance. They may have other medical problems. first cousins. People who have a pair of grandparents in common. For two first cousins, a parent of one first cousin is the brother or sister of a parent of the other first cousin. gene. Information needed for the body to work, stored in a chemical form on chromosomes. Changes or mutations in genes alter the information and this can change how the body works. Autosomal genes are in pairs: one from the mother, one from the father. The two genes of a pair are at matching places on a pair of
7 7 chromosomes. (As an analogy: a chromosome is like a book, a gene is like a story in the book, a change or mutation in a gene is like a missing or extra letter in a word in the story). genetic. Caused by genes, concerning genes. mutation. A change in a gene. Some mutations are not harmful. Sometimes when a gene is changed, its information is altered so it does not work properly. (As an analogy: a change or mutation in a gene is like a missing or extra letter in a word in a story). prenatal diagnosis. Test during a pregnancy for the presence or absence of a genetic disorder in the baby. sex chromosomes. The X chromosome and the Y chromosome. sickle cell anaemia. A genetic disorder caused by having a change (mutation) on both copies of the sickle cell gene. People with sickle cell anaemia can have attacks of severe pain or sudden life-threatening infections. The risk of inheriting a sickle cell gene with a change (mutation) depends on the ancestry of the person. Most affected people are born to parents who are both healthy carriers and have no affected relatives. spina bifida. A disorder of the spine. Severely affected people may have considerable physical disability. This disorder does not have a simple genetic cause. Tay-Sachs disease. A serious genetic disorder, fatal in early childhood. thalassaemia. A group of genetic disorders affecting the blood. The effects of thalassaemia depend on the particular thalassaemia gene which has a change (mutation), and on how many changed thalassaemia genes a person has. The risk of inheriting a thalassaemia gene with a change (mutation) depends on the ancestry of the person. Most affected people are born to parents who are both healthy carriers and have no affected relatives. This glossary is intended only for use by patients and families, with the genetic information to which it refers. This edition prepared in July 2005 Ref Glossary 16
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