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Autosomal recessive verses autosomal dominant retintis pigmentosa (RP)
Autosomal recessive retinitis pigmentosaAn autosomal recessive mutation may occur anywhere on the 44 autosomal chromosomes that comprise a person's genome (remember that humans have 46 chromosomes - 2 of them sex chromosomes, 44 of them autosomal). However, because each chromosome is part of a matching pair, the mutant gene will not be expressed as long as one of the two genes in the pair doesn't contain the altered gene. Conversely, if a person does not have a 'normal' gene among his or her chromosome pair, then the altered gene will be expressed.
In the first case, where a person has one normal and one altered gene, a person is said to be a carrier; in the second case, where no normal gene is present, the person is said to have autosomal recessive retinitis pigmentosa.
With carrier parents, neither parent is affected by retinitis pigmentosa (RP) so neither one will develop it during his or her lifetime. Nonetheless, the recessive trait for retinitis pigmentosa, while not expressed due to the presence of a 'normal' gene, is still part of the genome and may be passed to the next generation. In fact, with each child born to a carrier, there is a 50 percent chance of a carrier parent passing an RP mutant autosomal recessive chromosome to his or her offspring.
The result - the child will not develop retinitis pigmentosa unless his or her other parent also provides an autosomal recessive chromosome. In autosomal recessive RP, it takes both chromosomes of a chromosome pair for a child to have RP. As long as there is one normal copy of the gene, the child will only be a carrier.
Example
This is best illustrated by the following example. When both parents are carriers for the autosomal recessive RP gene, there are four possible results for each child that is born. The probabilities do not change with the birth of each subsequent child.For arguments sake, we will pretend that it is chromosome 2 of the 22 autosomal chromosomes that contains the autosomal recessive gene for retinitis pigmentosa. We will designate 2m for mom's chromosomes and 2p for dad's chromosomes. But because mom's and dad's chromosome pairs also have maternal and paternal chromosomes, they will be differentiated by the symbols i (maternal) and ii (paternal).
We will further designate 2mii (mom paternal) and 2pii (dad paternal) as the autosomal chromosomes that have the recessive gene for RP while the 2mi and 2pi contain normal genes. So, mom's chromosome 2 pair is represented by 2mi2mii and dad's chromosome 2 pair is represented by 2pi2pii.
When the egg (carrying either a chromosome with 2mi or 2mii not both) and sperm (carrying a chromosome with either 2pi or 2pii not both) meet during fertilization, there are four possibilities:
A closer look at the four possibilities: Affected means that the child will have autosomal recessive retinitis pigmentosa.
Generation 1
Four possibilities for 2mi2mii and 2pi2pii parentsOutcome
2mi2pi Normal. 25 % chance. The child does not have any autosomal chromosome RP gene (2mii or 2pii). Both Chromosomes are normal.
2mi2pii or 2mii2pi Carrier. 50 % chance. There is one good copy (2mi or 2pi) and one mutant copy (2mii and 2pii) of the gene in each case. The normal gene is expressed.
2mii2pii Affected. 25 % chance. The child will get retinitis pigmentosa. Both copies of the gene mutation for RP (2mii and 2pii) are present. No normal gene is present to be expressed.
*This probability table remains true for the birth of each child. The birth of one child does not influence the chance of the next child being normal, a carrier or affected.
As you probably see from the above example, a child with 2 parents who have autosomal recessive retinitis pigmentosa has a 100 % chance of getting the disease. This child then has a 100% chance of passing the altered genes on to the next generation.
Subsequent generations: The above symbols are used for the next generation (where 2mii and 2pii have the autosomal recessive gene for RP and 2mi and 2pi are normal). The below cases are based on the above generation 1 outcomes and a varied case. Affected means that the child will have autosomal recessive retinitis pigmentosa.
1st generation (from table above) and varied caseOutcome
2mi2pi (normal) and normal (2mi2pi) Normal. 100 %. No ii (altered) gene is present to be passed on to the next generation. Both parents have normal genes so all the children do too.
2mi2pi (normal) and carrier (2mi2pii or 2mii2pi) 2mi2pi (normal) and affected (2mii2pii)
2mi2pii or 2mii2pi (both carriers) and normal (2mi2pi) 2mii2pii (affected) and normal (2mi2pi) Carriers. 100 %. Offspring have a 2mii2mi, 2mii2pi, 2pii2mi or 2pii2pi. Remember that (ii) symbolizes the altered gene - which is present in each combination.
2mii2pii (affected) and carrier (2mi2pii or 2mii2pi) 50 % carriers. 50 % affected. Offspring (using carrier 2mi2pii as an example) have a 2mii2mi, 2mii2pii, 2pii2mi or 2pii2pii. Remember the ii symbolizes the altered gene - which is present 75 % of the time - in each case.
2mii2pii (affected) and affected (2mii2pii) Affected. 100 %. Offspring 2mii2mii, 2mii2pii, 2pii2mii, 2pii2pii. No normal gene to inherit - mom and dad supply only genes for autosomal recessive RP.
Autosomal recessive RP is the most probable explanation for seemingly isolated incidences of retinitis pigmentosa. While the absence of RP in a family history makes it almost impossible to trace inheritance patterns, spontaneous RP gene mutations are known to be a rarity.
Autosomal dominant retinitis pigmentosa gene
In autosomal dominant retintis pigmentosa, one of the chromosome pairs has been altered, but unlike autosomal recessive RP this gene is all that is required for the expression of retinitis pigmentosa gene. The normal gene is ineffective against overriding the affects of the mutant gene. A child with this gene will get RP.
A parent with the autosomal dominant gene has a 50 % chance of passing it on to each of his or her offspring. This RP dominant gene ensures that the resulting child will have retinitis pigmentosa.
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