Too many chromosomes

This question was submitted by my dad, who wanted to know what caused Down Syndrome.

At this point, I think it’s hard to deny we’re making great strides with Down Syndrome, both from a cultural and medical standpoint.

Just last week, the 2015 Special Olympic World Games wrapped up in Los Angeles after its arguably best year ever. Michelle Obama opened the games, and ESPN televised the ceremony¹. Special Olympics athletes, many with Down syndrome, set new world records².

From a medical standpoint, the gains for individuals with Down syndrome are also tremendous. A little over a hundred years ago, Down syndrome life expectancy was less than 10 years, but now people with Down Syndrome routinely live well past 50³.

Most of us are familiar with Down syndrome. Many, but by no means all, people with Down syndrome have a characteristic appearance and have challenged intellectual development⁴. Thanks to modern advances, Down syndrome patients live full, happy, productive lives.

But what exactly causes it?

Down syndrome is known as Trisomy 21 in medical and scientific circles because it’s caused by an extra copy of chromosome 21. The human genome is split into 23 chunks known as chromosomes, numbered 1-22; the 23^rd chromosome is the sex chromosome (i.e. X and Y chromosomes). A normal, healthy individual will have 46 total chromosomes in the average cell, one set of 23 chromosomes coming from the mother and the other set of 23 chromosomes coming from the father. People with Down syndrome have an extra copy of chromosome 21, giving them 47 chromosomes total.

That extra copy of chromosome 21 comes from an error occurring during a process known as meiosis, the process that makes oocytes (a.k.a. eggs) and sperm. Meiosis is different from normal cell division (mitosis) because instead of making two identical copies of a cell after dividing, the cell splits into two unique cells with half the number of chromosomes.

When oocytes and sperm fuse, they make a fertile cell with 46 chromosomes that develops into a fetus. This recombination of genetic information from generation to generation allows for the diversity we see in the human population and protects us from becoming vulnerable to genetic and infectious diseases.

Each oocyte or sperm is supposed to have only one copy of each chromosome, but the cell sometimes makes a mistake during meiosis. Sometimes an oocyte or sperm will get two (or no) copies of a particular chromosome, and we call this chromosomal nondisjunction. If an oocyte gets two copies of chromosome 21 instead of only one and it’s fertilized by a sperm, it will develop into a child with three copies of chromosome 21 (hence the name Trisomy 21), causing Down syndrome.

Getting the wrong number of chromosomes in a sex cell is much more common than many people think. A surprising number of pregnancies—1 in 5, at least—result in miscarriage, and medical researchers think that half of those miscarriages happen because of chromosomal nondisjunction⁵. Having the wrong number of chromosomes in an embryo is almost always fatal very early in pregnancy, and most of these miscarriages happen before the mother even knows she’s pregnant.

Animals are particularly sensitive to something called gene dosage, which means that we need two copies of each gene—no more and no less—in order to function normally. Many genetic diseases result from having only one functioning copy of a gene, or in the case of Down syndrome, from having three copies of all the genes found on chromosome 21. People with Down syndrome simply have too much of what they need from that chromosome in every cell.

Chromosome 21 is one of the only chromosomes we can survive with if we have an extra copy of it. Chromosomes are numbered based on their size; chromosome 1 is the largest chromosome and chromosome 22 is the smallest. Because chromosome 21 is so small compared to some of the larger chromosomes, the excessive genetic material from chromosome 21 isn’t fatal.

Trisomies with larger chromosomes produce diseases that are much more severe than Down syndrome. Patau syndrome (a.k.a. Trisomy 13), for example, causes severe nervous system and urogenital defects, and the few fetuses carried to full term perish only 4 months after being born⁵. Likewise, infants born with Edwards syndrome (a.k.a. Trisomy 18) have severe organ system defects and rarely survive past their first year⁵.

By comparison, Down syndrome is relatively mild. Although people with Down syndrome are likely to suffer hearing loss, vision problems, and leukemia^4,7, they can live long, full lives.

There is still much to learn about Down syndrome. That being said, people with Down syndrome now live over 40 years longer and have much happier lives than they did at the turn of the 20^th century. If we came that far last century, the next century should hold plenty of promise.

References

http://www.nytimes.com/aponline/2015/07/26/us/ap-us-special-olympics.html

http://www.npr.org/2015/08/03/428901750/after-9-days-special-olympics-world-games-come-to-a-close

http://www.who.int/genomics/public/geneticdiseases/en/index1.html

http://www.cdc.gov/ncbddd/birthdefects/downsyndrome.html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991414/

http://www.ncbi.nlm.nih.gov/pubmed/19212162

http://www.ncbi.nlm.nih.gov/pubmed/8197171