Down Syndrome (Trisomy 21) is a common cause of mental retardation. It is caused by nondisjunction during meiosis that leads to an extra chromosome 21 being present. Instead of having 46 chromosomes they have 47. Prenatal screening shows increased nuchal ridge on ultrasound (increased nuchal translucency) as well as decreased alpha feta protein (AFP) and increased human chorionic growth hormone (hCG) in the blood of the mother. Down Syndrome is associated with:
- Acute Lymphoblastic Leukemia (ALL)
- Atrial Septal Defects
- Simian crease (horizontal crease across palm)
- Facial abnormalities (Flat facial features & prominent & prominent epicanthal folds)
- Duodenal Atresia
Chromosomal Translocation is when non-homologous chromosomes “swap” sections. It is the abnormal form of crossover during mitosis or meiosis. Genetic material can be added or lost during this process. When genes are moved to a new area they may also be regulated by a new set of control mechanisms (like a new promoter) which will affect how much of the resulting protein is created. Here are some high yield examples which will be covered in the organ system sections:
- t(8:14) = Burkitts Lymphoma
- t(11:14) = Mantle Cell Lymphoma
- t(14:18) = Follicular Lymphoma
- t(8:21) = AML
- t(9:22) = CML
- t(15:17) = APL
Trinucleotide Repeat Expansion is where abnormal DNA replication causes a repetitive section of DNA to be enlarged. For example, a gene may have a certain 3 nucleotide code repeated a dozen times normally, but be repeated hundreds of times in a trinucleotide repeat disorder. It is as if the DNA replication machinery gets “stuck” on a certain section and repeats it too many times. The severity and age of onset of these diseases can be predicted by the number of repeats present (more repeats is worse). The highest yield disorders of this type are Huntington’s Disease (CAG repeats)and Fragile X Syndrome (a form of mental retardation with facial abnormalities).
Anticipation is when genetic disorders have an earlier onset in each subsequent generation. Anticipation is seen primarily in trinucleotide repeat expansion disorders and is due to the number of repeats increasing in later generations. This phenonmenon is observed because the presence of a high number of trinucleotide repeats increases the likelihood of errors during replication. In other words the mutation itself causes further mutation.