Human Genome Analysis Of Pakistani Population Reveals How Inactive Genes Affect Our Health

A massive genetic analysis of British-Pakistani populations has revealed much about the human genome. Getty

Every skill, emotion, and physical attribute that you and anyone in history has ever felt or had can be traced back to the twenty thousand tiny genes that make up the human genome. Until recently, it was believed that having an inactive set of genes, known as a "knockout" because the genes are figuratively "knocked-out" of the genome, could lead to serious health complications. Recently, however, researchers analyzed the genomes of around 3,200 British citizens of Pakistani descent and found that, not only are knockouts pretty common, but they also don’t always indicate poor health.

For the study, led by researchers from Queen Mary University in London and the Wellcome Trust Sanger Institute in Cambridge, the United Kingdom, a team of scientists analyzed the genomes of 3,222 healthy British-Pakistanis hoping to find knockouts present for studying the role they play in our health. The analysis revealed the presence of 781 knockout genes. When the team linked the genetic data to lifelong health records, they were surprised to find that an overwhelming number of these knockouts had no adverse effects on the volunteer’s health. This goes against the previous animal studies that correlated knockouts with adverse health risks, such as sterility and serious illness, Science reported.

“We suggest that many previous genetic studies may have overestimated or inaccurately estimated risk of disease given a genetic variant, when taken into larger populations.” Professor David van Heel, who co-led the study at Queen Mary University of London, said in a recent statement.

At conception, we inherit two sets of each gene, one from each parent. Every human has the same set of genes, but while we may all have the gene for eye color, slight variations in this gene give some people blue eyes and others brown. In addition, carrying the genetic variation for blue eyes does not mean that you will have eyes of that color. However, it does mean your children might, depending on what matching set they inherit from their other parent.

Sometimes when an inactive gene is inherited from one parent, the active version we inherit from another parent will compensate for the loss, and thus no effect is seen. When we inherit two inactive genes, a ‘knockout’  occurs, Science reported. While knockouts are rare in the general population, their occurrence is more popular in populations that have a higher tendency to marry family members. This is because relatives are more likely to have the same inactive genes than two people who share no relation. Therefore breeding between relatives increases the offspring’s chances of inheriting both inactive genes, Medical Express reported. In Pakistani culture, marriage between family members is not as taboo as it is in other cultures, and many of the study participants had parents who were first cousins, Science reported.

Typically, knockout gene study is conducted on mice genetically edited to render certain genes purposely inactive. These “knockout mice” play an important role in researching different kinds of cancer, obesity, heart disease, and many other conditions, as reported by the National Institute of Health. Unfortunately, results from rodent study do not always indicate the same for human health. For example, one study found mice become sterile when the gene PRDM9, which helps shuffle chromosomes during the formation of eggs and sperm, is deleted. However, the same has not been found to be true in humans. One healthy woman who participated in the study completely lacked PRDM9 and still went on to reproduce. This research team also observed that only nine of 38 volunteers lacking genes whose absence had previously been linked to serious diseases showed any signs of illness.

The scientists ultimately concluded that of the 20,000 genes in the human genome, only 3,000 may actually be essential. The rest could be knocked out and it would still have little to no affect on our health. Based on this conclusion, the team urges doctors to avoid rushing to gene deletion for their patients because knockout genes are not always harmful.

The results are changing what we know about genetics and the human genome, but the team is hopeful that eventually a better understanding of knockouts could have medicinal uses. For now, researchers are working on building a database for human knockout genes, Science reported. When the database opens in mid-summer, they will be able to find individuals who already have this gene deletion rather than having to purposely knock out a gene in a mouse. Hopefully, this will give them a better idea of the gene’s function.

Source: Narasimhan VM, Hunt KA, Mason D, et al. Health and population effects of rare gene knockouts in adult humans with related parents. Science . 2016

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