Photo: Bloomberg
Photo: Bloomberg

Opinion | Genetic matchmaking can improve medical outcomes

With the rapidly falling cost of sequencing the whole human genome, it should be relatively easy to undertake a widespread genetic analysis of all the endogamous groups in India to correlate genetic markers unique to those specific groups with symptoms that have a high rate of occurrence

Recent studies of the whole human genome have proven that the entire population of Ashkenazi Jews in existence today descended from no more than 350 individuals who lived 800 years ago. The genetic similarities among members of this sect were found to be so acute that everyone in the community is, at the very least, the 30th cousin of everyone else. This level of consanguinity only occurs when a relatively small community is kept isolated for geographical or social reasons resulting in large scale and persistent in-breeding. Population bottlenecks such as this have been observed among the Finns, the French Canadians in Saguenay–Lac-St.-Jean, and in orthodox religious groups such as the Amish and the Hutterites.

Communities with population bottlenecks are highly susceptible to genetic diseases. The Ashkenazi Jews, for instance, commonly suffer from Tay-Sachs, cystic fibrosis and Gauchers disease. Due to a historically high reproductive rate among the relatively small number of individuals that comprise the community, rare mutations that might have been dormant in founder individuals begin to express themselves over time among their descendants, with dramatically increased frequency the longer the community remains endogamous.

Mutations, of themselves, are not uncommon in the general population. When an offspring inherits a copy of a recessive gene from only one parent, it could go through its entire life without displaying any symptoms of the disease. It is only when a child inherits a copy of the same mutation from both parents that the disease surfaces. In communities with population bottlenecks, there is a significantly higher chance that both parents will carry the same recessive mutation.

A number of inherited diseases have been identified to commonly exist in various Jewish communities such as the Ashkenazis. As abortion is generally unacceptable among orthodox Jews, prenatal screening is largely ineffective as a means to prevent affected foetuses from going to full term.

To work within these religious constraints, Rabbi Josef Ekstein, a New York Jew, established Dor Yeshorem in 1983. The organisation used genetic techniques to screen members of the Jewish community from as early as when they were in high school, hoping to identify those that carried recessive genes for Tay-Sachs, cystic fibrosis or Gaucher’s.

Armed with information about their own genomic mutations, these schoolchildren were now equipped to determine, even before they started dating, whether the offspring they might have with the persons they intended to date are likely to be afflicted with one of these diseases. As unromantic as this might sound, in communities with rigid religious and social norms, genetic matchmaking is perhaps the only way to avoid the proliferation of genetic diseases.

India is home to more than 40,000 jatis as well as various other tribal groupings. Many of these groups follow, to this day, strict rules of endogamy that prevent them from, or at the least frown on, marrying anyone outside their group. We have only relatively recently begun to test these groups for genetic similarity.

Early results indicate that genetic differentiation between groups in India is likely to be as much as three times higher than differentiation within populations in Europe. This is a clear indicator of the existence of population bottlenecks in India similar to those among religious sects in the West.

As population bottlenecks are themselves indicators of genetic disorders, it stands to reason that the endogamous populations of India are likely to be rife with inherited diseases. However, as there has been little systematic research into identifying the genes responsible for disorders common to Indian endogamous groups, not much is known about which groups are likely to have what mutation. The little that we do know indicates that this is research worth doing.

For instance, we know that there is a high probability that Vysyas carry a recessive mutation in their genome that results in reduced levels of butylcholinesterase in their body. If anyone with low levels of this protein is given anaesthesia, there is a good chance that they could go into prolonged, potentially fatal, muscular paralysis. No doubt numerous other such genetic insights will surface if we begin to look for them in other endogamous groups. A good proportion of these insights could well mean the difference between life and death.

With the rapidly falling cost of sequencing the whole human genome, it should be relatively easy to undertake a widespread genetic analysis of all the endogamous groups in India to correlate genetic markers unique to those specific groups with symptoms that have a high rate of occurrence. This will give us a significant opportunity to improve medical outcomes by simply studying rare recessive traits in specific communities.

If we can make progress in this direction, we should be able to introduce genetic matchmaking into the arranged marriage workflow so that along with horoscopes, parents are encouraged to match whole genome reports to ascertain whether their as yet unborn grandchildren run the risk of inheriting deleterious double recessive mutations. Or perhaps someone will build an app that automatically incorporates your genetic report into your online profile and only allows you to swipe right if the person you are about to “like" is genetically compatible.

Rahul Matthan is a partner at Trilegal and author of Privacy 3.0: Unlocking Our Data Drive Future. Ex Machina is a column on technology, law and everything in between. His Twitter handle is @matthan.

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