Genetics as it Relates to down Syndrome

Down syndrome is a genetic disorder caused by the presence of an extra copy of the twenty-first chromosome in the human genome.  This condition, more properly called trisomy 21, causes severe mental and physical disabilities, and it occurs in about 1 in every 900 births.  The two most ubiquitous symptoms of the syndrome are a slowing and stunting of mental development, resulting in patients with average IQ scores around 50, and stunted growth.  However, the actual measurement of the syndrome’s effect on IQ is somewhat controversial, as several non-mental factors associated with the syndrome, such as visual and auditory impairments that occur in a disproportionately high number of patients can lower the score without being actual indicators of low mental capacity. 

Genetically, trisomy 21 is defined as a meiotic nondisjunction.  Essentially, this means that in the process of meiosis (the production of sex cells or gametes), both members of a chromosome pair end up in one gamete.  Ideally, one member would have ended up in each gamete.  This results in one gamete with  two copies of the chromosome and one gamete with none. 

When the gamete with two copies joins with another parent’s normal gamete, the resulting zygote has three copies of the chromosome.  In most cases, this is immediately deadly.  However, nondisjunction can be survivable in the cases of trisomy 18, trisomy 21, and when extra copies of chromosomes X or Y are present.  In all survivable cases of nondisjunction, however, disorders occur with varying degrees of severity.  Trisomy 18 and trisomy 21 are much more severe than nondisjunction events affecting chromosomes X or Y.

One other way that trisomy 21 can occur is in a mosaic situation, when some cells have the trisomy and some do not.  This occurs after fertilization and is based in mitosis rather than meiosis.  Early in cell division, a mutation can arise which causes one lineage of daughter cells to exhibit trisomy 21.  This is a mutation which has nothing to do with the meiosis of parental gametes.

Down syndrome can also arise meiotically via a slightly different pathway, in which a phenotypically normal parent has a chromosome 21 which is attached to another chromosome.  This increases the probability that chromosome 21 will improperly copy itself when undergoing meiosis.

Finally, Down syndrome can arise from a duplication mutation of the genes along chromosome 21 that cause the syndrome.  In effect, this is a rare form of Down syndrome in which there is not actually a third copy of chromosome 21, but merely a few extra genes that happen to be combined in such a way that they mimic the effect.