This is a fascinating book about our chromosomes and how they affect our lives. Each chapter is devoted to one chromosome, hence the 23 chapters. Huntington's Disease is discussed in Chapter 4, but this book is about much more than just diseases. It examines the history of mankind from a genetic perspective, and shows how our genes affect us in many ways.
The introduction provides an excellent foundation to help a lay person understand genetics. On page 7, Mr. Ridley says, "Imagine that the genome is a book.
There are twenty-three chapters, called CHROMOSOMES.
Each chapter contains several thousand stories, called GENES.
Each story is made up of paragraphs, called EXONS, which are interrupted by advertisements called INTRONS.
Each paragraph is made up of words, called CODONS.
Each word is written in letters called BASES."
The gene for Huntington's Disease was found in 1993. It is located on the top of chromosome 4. However, Mr. Ridley emphazed that the gene does not cause the disease. Everybody has the gene, except for people who have Wolf-Hirschhorn syndrome, which is very rare and very serious. Its victims die young, so the gene itself is something that everybody needs.
The sufferers of Huntington's Disease have a mutated form of the gene, where the repetitions of the CAG sequence are higher than normal. According to Mr. Ridley, most people have about 10 to 15 repeats. As long as the repeats are 35 or fewer, the person will not manifest HD. Persons with 36 to 38 repeats may or may not ever show signs of the illness, but they may have affected children. If the repeats are 39 or higher, the person has a 90 % chance of manifesting severe HD symptoms by age 75.
Most of us who are familiar with Huntington's Disease have heard that it is caused by an excessive repeat of the CAG sequence. However, we probably don't know what that actually means. Mr. Ridley explains that the words in the genome are all three-letter words, and only four letters are used in those words. They are A, C, G and T, which stand for adenine, cytosine, guanine and thymine.
Each three-letter word codes for an amino acid in the manufacture of the protein controlled by the gene. The amino acid coded by CAG is called glutamine. Amino acids form proteins, and the protein containing this sequence of glutamines is called huntingtin. The repetition of the word CAG in the middle of the gene results in a long stretch of glutamines in the middle of the huntingtin protein. Exactly how this long stretch of glutamines causes Huntington's Disease is unknown, but generally speaking the more glutamines there are, the earlier in life the disease begins, and the more severe are its manifestations.
It is known that in some cases, the disease begins earlier or may be more severe in the children of an HD patient than in the patient himself. This is called anticipation and is particularly likely to occur when the HD affected parent is the father, and especially when the affected parent has a relatively large CAG repeat number. The longer the repetition of CAGs, the longer it is likely to grow when copied for the next generation. Mr. Ridley shows how this might happen. He first repeats cag 6 times in a sentence (cag cag cag cag cag cag), and those are easy to count. He then repeats cag 36 times in the sentence, and as you might expect, those are harder to count. He explains that the more repeats there are, the more likely it is that the copying mechanism will insert an extra one.
Spontaneous appearance of the Huntington's mutation seems to happen when a parent has a CAG repeat number just below the threshold and then it jumps above the threshold because the copying mechanism accidently inserted an extra one or changed a similar one to CAG. If the person had, for example, 35 CAGs, followed by a CAA, then two more CAGs, and the CAA accidently changes to a CAG in the copying process, then the child would have 38 CAGs.
I read this book because it was recommended to me by a student at the University of Chicago who was required to read it for Biology and was writing a paper on Huntington's Disease. I was primarily interested in the chapter on Huntington's Disease, but I actually found the entire book very interesting. It is written in non-technical language, so it is easy to understand by non-scientists like me.
Created and maintained by Renette Davis. Send comments to Renette by clicking here.
Created: July 4, 2002
Last update: Dec. 1, 2010