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About Genetics - for parents |
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About Genetics - for parents |
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Chromosomes, Genes and DNA : What is a Karyotype? : Inheritance Patterns : De-novo : Genetic Testing : The Full Picture
The majority of lissencephaly cases appear to be genetic. It is either an inherited condition or due to a new random genetic mutation. This page is an overview on genes, chromosomes and inheritance. It is to be used only for education purposes and not for the medical care of an individual. Always check with your Geneticist if you have queries about your particular situation. Remember, a genetic condition is not necessarily an inherited condition.
What are Chromosomes, Genes and DNA?
In every living cell in our bodies there is a nucleus. The nucleus is the part of the cell that contains the 'recipe' to create us exactly as we are. In every cell of our body there are 46 chromosomes - they are the structures that hold our genes. These 46 chromosomes occur as 23 pairs. We get one of each pair from our mother in the egg, and one of each pair from our father in the sperm. The first 22 pairs (known as the autosomes) are labelled 'chromosome 1' (the longest) to 'chromosome 22' (the shortest). The last pair are called the sex chromosomes labelled X or Y. Females have two X chromosomes (XX), and males have an X and a Y chromosome (XY).
Overall, the 46 chromosomes contain a total of around 40,000 genes. Genes are the individual instructions that tell our bodies how to develop and keep our bodies running healthy. The genes are made from DNA which is a complex chemical made up of four basic ingredients called bases.
Everyone should have 46 chromosomes in every cell of
their body. If a chromosome or piece of a chromosome is missing or duplicated, there are
missing or extra genes respectively. When a person has missing or extra information
(genes) problems can develop for that individual's health and development.
Each chromosomes has a p and q arm; p (petit) is the short arm and q (next letter in the alphabet) is the long arm. The arms are separated by a region known as the centromere, which is a pinched area of the chromosome.
The chromosomes can be seen under a microscope. The chromosomes look like strings with light and dark 'bands'. Each chromosome arm is defined further by numbering the bands, the higher the number, the further that area is from the centromere.
For a condition like Miller-Dieker Syndrome , the affected chromosome is number 17, the specific region is on the short (p) arm at location 13.3. This is normally written 17p13.3. The gene that is directly responsible for the smooth brain on 17p13.3 is called LIS1.
A karyotype is a highly magnified image of all the chromosomes from one cell.
Normal Male Karyotype - a female would have two X's instead of an X and Y
In a karyotype the chromosomes can appear bent or twisted. This is normal and is simply reflecting how they are sitting on the slide. Chromosomes are flexible structures made up of DNA. The coding order of that DNA makes up the genes. If you were to pull out all the chromosomes into long strands of DNA there would be over 7 feet of DNA in each cell! That's about 80 billion miles of DNA in the average human adult!
About Inheritance - Dominant, Recessive and X-linked Inheritance traits
Genes work in different ways. The autosomes (chromosome 1 to 22) occur in pairs. Some characteristics require both gene pairs (i.e one from each chromosome) to be present and correct for them to operate correctly - these are Dominant genes. If one of the pairs of genes is missing or damaged the other matching gene is unable to make up for the deficiency. In this instance, the resulting inheritance pattern is called Autosomal Dominant (AD). Some dominant traits are inherited from a parent but some are de-novo (see below).
Some characteristics only require one gene to work correctly out of the pair that are available - these are Recessive genes. If one gene from the pair is missing or becomes damaged a person is unaffected (and is a carrier), however if both genes are missing or damaged a person is affected. The resulting inheritance pattern is called Autosomal Recessive (AR). Generally, for a child to have a recessive disorder, both parents must 'carry' a missing or damaged gene and pass both these on to their child. As both parents carry a good and bad gene, the probability that a child will be affected is 25%. The probability of being a carrier is 50% and of being unaffected is 25%.
A third type of inheritance pattern occurs due to one of the chromosomes that define our gender, the X-chromosome. Males only have one X-chromosome, whereas females have two. If there is a damaged or missing gene on the X-chromosome in a girl, it is unlikely to have an effect as she will have a good gene on her other X-chromosome. However, if a boy, has a damaged or missing gene on his only X-chromosome, he will have an inheritance pattern that is called X-linked (XL). Generally X-linked cases are carried by a female (the mother) and passed on to some of her sons. However, this isn't always the case as some X-chromosome abnormalities are de-novo (see below). Where the trait is inherited there is a probability that the child will be an unaffected boy (25% chance), a carrier girl (25% chance), an unaffected girl (25%) or an affected boy (25% chance).
It is possible for a genetic counsellor to gauge what the inheritance pattern is just by asking about your present and past family members to see if there were other cases.
It is important to note that most chromosome abnormalities occur as a accident in the egg or sperm. In this case the fertilised egg or sperm multiplies and therefore every cell in the body has the abnormality. Some abnormalities can happen after conception and individuals can have a mosaicism (some cells with the abnormality and some without). So a de-novo (new) mutation is not inherited, it just happened and generally is unlikely to happen again. Many (but not all) cases of ILS are de-novo.
Testing for a particular condition will first start with a clinical assessment to try to ascertain what the suspected condition or the range of conditions might be. An MRI or CT scan will be used to help provide the clues to what to do next.
Genetic testing is a broad and complex field. However there are three levels of testing that may be applied:
The big problem for geneticists is what to do if the test results are negative or if they don't know where to look. The problem of identifying new genes is huge. Where should they start looking? There are 46 chromosomes, with up to a total of 40,000 genes, any one of which could be damaged or missing. This is worse than looking for a needle in a haystack, it is more like looking for a needle in a haystack in the whole of the UK!
So, for conditions where genes or chromosome regions have been identified tests can be applied relatively easily, but for those that haven't yet been identified there is a huge amount of research still to be done.
To obtain the full picture about your child's condition the following needs to be established:
An overview of the genetics of Lissencephaly (and polymicrogyria) can be found at the Geneclinics website.
This has been a simplified description of chromosomes and inheritance. Genetics is full of exceptions and results that can be difficult to interpret. Always check with your Geneticist.
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This page last updated: 15/11/03