Knockout Genes In Human Population

An example of genetic variance across different regions of the world (picture from Wikimedia Commons)

      In the quest to figure out how specific genes work in laboratory mice, creating "knockout" mice is usual the way to go. In this practice, a specific gene is targeted and eliminated to see how it affects its functioning. For obvious reasons, creating "knockout" humans is not a feasible way to study the effects of missing genes in humans.

      Recently, there has been a push by researchers to look for the effects of naturally occurring knockout humans. One such study focuses specifically on individuals from Pakistan. This study notes the prevalence of knockout humans as a result of consanguineous mating practices in a group of Pakistanis participating in a long-term study of heart disease and diabetes. Researchers were intrigued to find that the absence of some genes seemed to have no negative affects on their health; furthermore, researchers concluded that such knockouts help explain why some drugs are more effective than others in terms of a person's individual genome.

     Overall, there is now multiple calls for a Human Knockout Project to document such findings in a single database. As the picture above helps illustrate, genes vary across populations; thus specific drugs may have varying efficiency in their modes of action based on the overall genetic composition of a population. Hopefully such a database drawn from large population studies would lead to a more personalized medicine approach to treating certain illnesses. This is relevant now, especially with population genetics being the subject of our current lectures.

Intro to Knockout Mice

Original Article

New Light on Disease Causing Genes

According to the article published by the New York Times, “In Iceland’s DNA, New Clues to Disease-Causing Genes,” scientist in Iceland have managed to sequence and analyze the genome of an entire single population.  They have gathered and infer the genomes of more than 100,000 Icelanders and through this information discovered a host of previously unknown gene mutations that may play roles Alzheimer’s, heart disease, and gallstones.  A group of researchers from Decode presented a mutation on eight people with a gene called MYL4 and medical records showed they also had early onset on atrial fibrillation.  Another mutation found was one that influences the level of a hormone that stimulates the thyroid glands.  When Icelander’s inherit this gene through their mothers, more hormones are made.  However, when inherited from their father, they make less.  

The research team found a rare mutation called ABDB4 that raises risk of gallstones and also one called ABCA7 as a risk factor for Alzheimer’s disease.  According to Gilian McVean, a geneticist at the University of Oxford, said this discovery is a rare and “a bit of a holy grail for genetics”.  Scientist usually search for causes by seeking those who lack the gene; the Icelander’s study seeks the gene and the specific mutation. The team of researchers looked for a human knockout gene and found a large amount in nearly 8 percent of the population.  With a technique called imputation, researchers claim to be able to ascertain full genomes of those who have not been examined.  Current policy does not allow Icelander’s to access or be informed of their genetics results.  However, the genetic diversity of Iceland is very low and makes it easier for researchers to detect genetic variants.

I found this article to be quite interesting because the amount of data it provided can help discover causes and possible treatments in the future.  With the changing world of genetics, the possibilities of knowing or not knowing of a chance of having a disease becomes a choice.  With that choice comes preparation for if or if not the disease comes to light.  One thing about this article I don’t agree with is that Icelander’s are not allowed the results of their genetics test.  It is their medical record and I feel everyone should be entitled to their records.  Hopefully this changes one day.