genetics - Linkage and LD: quantitative or qualitative?

Linkage disequilibrium (LD) occurs when there is a non-random association or correlation between genotypes. Note I used the word correlation; this is a quantitative trait.

Some genotypes may well correlate perfectly (R=1), i.e. they are always inherited together. Others may not be in 'perfect' linkage (e.g. R=0.9), but are still considered to be in LD because there is a strong correlation between the genotypes (I think 0.8 is generally seen in published papers as the 'cut-off').

The correlation coefficient is derived from the D' value - this (simply) denotes the observed vs. expected frequencies of the genotypes (whether they are in linkage or not). Therefore either value can be used, but I think it is more common (and more interpretable) to express the correlation coefficient (or to be more precise, the coefficient of determination, R^2).

If you'd like an example: I might be interested to know if any SNPs are in LD with rs10757278 (located on 9p21, associated with heart disease). Using SNAP (by the BROAD) I can input my search, choose my options (e.g. use 1000 genomes data, and an R^2 cut-off of 0.8) and search. ~5 SNPs are found to be in 'perfect' LD (R^2=1), but a further ~40 are still considered to be in linkage with the input-SNP because their R^2 values are above 0.8.

So in summary, both statements can be used correctly, but it is always more informative to state the degree of linkage (otherwise it might be assumed they are in perfect correlation).

evolution - Why is the Kakapo more attracted to humans than its own kind?

The male kakapo (Strigops habroptila) in that video is called Sirocco. Kakapo were (and still are) very close to extinction, so in the 1980s the Kakapo Recovery Programme was launched. As part of this programme, rangers monitor all known kakapo in the wild, visiting their nests and generally ensuring they are in good health. When Sirocco was a young chick, a ranger discovered him in his mothers nest with severe breathing problems. He was brought back to the Kakapo care hut and raised by humans. As a result of this, he imprinted on his carers (see his website!).

Imprinting is common in birds, and takes several different forms. The most well-known form is filial imprinting, where young birds (and some other animals) develop a strong fixated image of who their mother is. They then learn their behaviour almost exclusively from the animal they fixated on. This is well studied in geese, for example by Konrad Lorenz.

However, Sirocco was demonstrating sexual imprinting. This is where young animals (including humans, see e.g. Bereczkei et al., 2004) learn which characteristics are sexually desirable by fixing an image of their parent(s). In Sirocco's case, he imprinted on a human and subsequently saw humans as his species, and therefore potential mates.

The exact purpose of sexual imprinting has been widely discussed (e.g. see Immelmann, 1972). Lorenz suggested that it allowed animals to recognise their own species. However, some imprintable birds will show a preference toward individuals resembling the one they imprinted on, but when introduced to their own species will still recognise them as potential sexual partners. It may therefore be the case that imprinting allows a juvenile firstly to supplement a genetic predisposition toward its own species, but secondly to recognise closely related and less related individuals. Bateson (1978) suggested that this would enable a sexual strategy of choosing mates which are sufficiently unrelated so as not to cause inbreeding depression, but sufficiently related so as not to cause outbreeding depression, and he found an example which bore out the predicted behaviour in Japanese quails.

Sirocco seems not to have the genetic ability to recognise his own species, and according to his website does not associate with other birds.

human biology - What part of food gives the blood red color?

The red colour of blood isn't actually to do with food at all. The primary purpose of the blood is to carry oxygen to all the cells that require it to release energy. Red Blood Cells are filled with an iron containing pigment called haemoglobin. When it has oxygen bonded to it, haemoglobin has a bright red colour - it is this that gives blood its red colour.

In terms of how food enters the bloodstream, it is first broken down into extremely small constituents. This is done by mechanical action (i.e. chewing and the squeezing movement of your digestive system) and by chemical action through the use of enzymes. Enzymes are proteins that are secreted by various glands in the mouth (and are therefore contained in saliva), stomach and both intestines. These chemically break large food molecules down into small products such as glucose (sugar) and amino acids (protein-building blocks) amongst other things. These then move across the wall of the intestines and into the bloodstream, which are separated by only one cell:

Unfortunately that's the best image I could find. The intestine is everything outside of the pink layer (which is the wall of the intestine). The small molecules are able to pass through the pink layer and straight into the blood stream. The picture shows a fold in the wall of the gut, which increases its surface area so allows more molecules to diffuse across.

molecular biology - How are the boundaries of a gene determined?

I know of only one naive approach to determining the boundaries of a gene : RACE-PCR. There are two kinds, 3' and 5' RACE, which allow to find the respective extremities.

The rationale is the following :

• You perform a reverse transcription of the transcript of interest using a specific primer. At this step you have a specific single stranded cDNA.




• Then you add a stretch of identical nucleotides called the homopolymeric tail in 5' of the cDNA.




• Finally you perform a PCR using one specific primer and one universal primer that recognizes the homopolymeric tail. You can sequence your amplified cDNA and find where it is located in the genome with a 1 bp resolution.

For the 3'RACE, the concept is the same but the poly-A tail is used instead of generating it yourself with the terminal transferase.

See this paper for a detailed protocol :

Sambrook J, Russell DW. 2006. Rapid Amplification of 5’ cDNA Ends (5'-RACE). CSH protocols 2006.

Also, the corresponding wikipedia article gives you more details about what is happening at each step, but beware, there is an error : it is said that for the 5'RACE, the terminal transferase appends the homopolymeric tail in 3' while it appends it in 5'

human biology - Are there any situations in which phenylephrine is preferred to pseudoephedrine?

Yes, in all clinical situations where you need pure vasoconstriction without heart rate acceleration (mostly valid for iv administration route).

The classical example would be in the operative setting. If the patient is in a hypotensive state due to hypnotic drugs, opiates, etc. and has atherosclerosis, you will prefer a drug that will reverse the hypotension without an increase in heart rate, i.e phenylephrine. The reason is that an increase in heart rate will shorten the duration of diastole, which will therefore shorten the time interval where the coronary arteries are perfused. Moreover, an increase in heart rate also means an increase in heart oxygen consumption. The end result will be an imbalance between oxygen input and requirement, i.e ischemia and potential heart infarction.

Conversely, if you have a patient with aortic valve insufficiency (regurgitation), you will prefer ephedrine (or any drug with beta 1 activity), because you will be aiming at shortening the available time for regurgitation to occur.

dna sequencing - Is there a detectable amount of bacterial DNA in the blood of infected persons?

Everything depends upon the infection and on the general immune status of the patient.

Generally, the prerequisite for DNA to freely circulate in the blood is the presence of bacteria themselves in the blood (bacteraemia). This means that the infection left its original site (where it is usually kept isolated from the blood flow by the immune system). Depending upon the body reaction to this breakthrough, sepsis and/or SIRS can be the consequences.

Under these conditions (not necessarily as severe as sepsis, but in case of proven bacteriemia), the bacteria cells get attacked by the immuno cells, that leads to their eventual lyzing and releasing their content to the blood.

PCR can be used as a method to prove the existence of bacterial DNA. (Here is a publicly available paper on this topic).