Monday, July 16, 2007

When English Majors Write About Genetics

Our favorite newspaper is at it again.
Williams syndrome rises from a genetic accident during meiosis, when DNA’s double helix is divided into two separate strands, each strand then becoming the genetic material in egg or sperm. Normally the two strands part cleanly, like a zipper’s two halves. But in Williams, about 25 teeth in one of the zippers — 25 genes out of 30,000 in egg or sperm — are torn loose during this parting. When that strand joins another from the other parent to eventually form an embryo, the segment of the DNA missing those 25 genes can’t do its work.
A brief consultation of even, say, Wikipedia would tell this otherwise well-meaning author- who, by the way, apparently writes about science for a living:
During meiosis, the genome of a diploid germ cell, which is composed of long segments of DNA packaged into chromosomes, undergoes DNA replication followed by two rounds of division, resulting in haploid cells called gametes. Each gamete contains one complete set of chromosomes, or half of the genetic content of the original cell.
For those of you reading at home- since meiosis is probably not on the top of your reading list- I remind you that like most stable DNA structures, chromosomes are double-stranded. You start with a cell containing 46 chromosomes- two copies of each 23 chromosomes. They duplicate; the cell has 92. The cell divides, then divides again. You end up with four cells, each of which has 23 chromosomes.*

At no point does the DNA unzip one strand from another in order to put one strand in each new cell. And for people who would like to say 'But it's a little error! Why do you care?'... because it's the writer's job to get it right. It's like saying President Bush regularly wears an Alf tie to signings. Easily checkable, and wrong. But anyhow. On to the interesting stuff.

What actually causes Williams Syndrome is defective recombination.
Meiotic recombination between polymorphic markers proximal and distal to the [7q11.23 1.4 Mb] deletion has been documented, suggesting that unequal crossing over between homologous regions is the mutational mechanism in most cases.16 17 However, the absence of recombination in other families suggests that intrachromosomal rearrangements may also occur. The presence of a genomic duplication at the deletion breakpoints may act as a hotspot for the recombination events causing Williams syndrome.
All human cells are supposed to contain 46 chromosomes total. Many common conditions, including Down's Syndrome and various trisomies, are caused by having 47.

Chromosomes are paired off during meiosis: of the 23 kinds of chromosomes, let's say each has an A and a B: 1a and 1b, 2a and 2b, etc. Since an egg has 23 chromosomes and a sperm also has 23 (in normal gametes), let's say A is inherited maternally, while B is inherited paternally.

During meiosis, the A and B chromosomes are stuck to each other (here's a very cool picture). This is part of a mechanism to make sure each new cell gets the right set of DNA- a correct 'genetic complement' . While they're stuck together, both strands of the chromosomes break through both strands in certain places. This enables, say, the top 'inch' of A to switch with the top 'inch' of B. There are certain places along the chromosomes where they don't usually break; think of them as armor-plated bits. One theory is that this prevents important genes from getting bits missing in the middle: if it can't break in the middle of a gene, it can't stick back together wrong.

Recombination is an important mechanism for genetic variation. Say that genes are colors and A1 has a pattern that goes red, blue, blue, orange, red, while A2 has a pattern of yellow, blue, blue, green, yellow. If they both break between the blues and then re-combine differently, you would get one (call it A1a) that was red, blue, blue, green, yellow and another (A1b) that was yellow, blue, blue, orange, red. Both of these are called non-parental genotypes: neither A1 nor A2 had this pattern originally.

Now here's what the author was trying to say. Imagine that A1 breaks after both blues, but A2 breaks between the blues, and then they recombine. You get A1a of red, blue, blue, blue, green, yellow and A1b of yellow, blue, orange, red. A1b is missing a chunk because of improper recombination. That's how people get Williams- a chunk with 25 genes is lost from somewhere in the middle of the chromosome, and the truncated chromosome is inherited by the child.

As a side note, if I were going to say that DNA got unzipped, I'd think the teeth would be individual bases. Not genes. Yes?

*Except for that weird thing where the egg goes through Meiosis I but only partly through MII, and then sheds its spare 23 chromosomes once fertilized. So the sequence is a bit off. But the principle holds.