Re: can linkage analysis be included in nanotechnology?

Your question is essentially about definitions of a few terms. In science, the usage of terms evolves a bit, but I think that you would find widespread agreement about these definitions.

1. Linkage analysis:

Genetic linkage refers to the failure of particular traits to show independent assortment in breeding experiments. The concept of genes as units of inheritance originates with Mendel. He found seven different single-factor traits in peas (tall or short plants, flower color, etc.). For each of these traits, there were two alleles that produced very different phenotypes. In two-factor crosses in which allelic differences for two different traits were segregating, he found that the traits assorted independently of each other.

Using contemporary notation, the cross of Aa x Aa produces a 3:1 ratio of phenotypically A to phenotypically a progeny. This is really a 1:2:1 ratio of AA:Aa:aa.

If two factors are involved, Mendel observed that the cross of Aa Bb x Aa Bb produced a 9:3:3:1 ratio of the following phenotypes: A B, A b, a B, and a b. This is exactly what is expected if both factors sort independently during meiosis.

After the rediscovery of Mendel, it was not long before the discovery of pairs of traits that failed to show independent assortment. This phenomenon was referred to as "linkage."

Suppose that AA BB is crossed to aa bb to give Aa Bb. Imagine that Aa Bb is crossed to aa bb (a testcross). We might observe 40% A B, 40% a b, 10% A b and 10% a B. The two parental types are present at a frequency of 80% and the two nonparental types are present at a frequency of 20%. This is considered 20% recombination or 20% crossing over, and gives a measured genetic distance between A and B of 20 centiMorgans (cM).

The term "linkage analysis," as described above, applies exclusively to the interpretation of breeding experiments, and not to any technique involving the manipulation of DNA.

Please see any basic genetics book, for example "An Introduction to Genetic Analysis" by Griffiths et al.:

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.TOC

2. Genotyping:

This term applies more broadly to any technique that can be used to determine the genotype. Note in the discussion above that we cannot directly determine the genotype of all individuals from crosses involving a recessive trait. Individuals that are AA appear phenotypically identical to individuals that are Aa for morphological traits.

One method of genotyping would be progeny testing. An individual that is either AA or Aa is crossed to aa. If there are any aa progeny, the individual being tested was Aa; if not, the individual being tested was AA.

You mention bands, as in electrophoresis of DNA. Some methods of genotyping are based on the analysis of DNA from individuals. Because DNA from AA individuals is different from DNA from Aa individuals, no trait is truly recessive at the molecular level.

3. Nanotechnology

This is a relatively new term referring to the development of materials and devices on an atomic or molecular scale. The development of materials or devices smaller than 100 nanometers is generally considered nanotechnology.

A nanometer (nm) is a billionth of a meter (10^-9 meter). Similarly, a nanogram is a billionth of a gram (10^-9 gram). The concentration of DNA in samples loaded onto gels are often given as nanogram/microliter. One nanogram/microliter is 10^-9 g/10^-6 l. This is the same as one microgram/milliliter (10^-6 g/10^-3 l) or one milligram/liter (10^-3 g/l).

Using a small unit to measure a small amount of a substance is different from building a material or a device that is smaller than 100 nm (like a buckyball).

I think that it is fair to say that while it might be possible to use DNA as part of a nanoscale device, routine manipulation of DNA using chemical methods is not nanotechnology.

Yours,

Paul Szauter
Mouse Genome Informatics