March 16, 2007

Considering Consanguinity (Inbreeding)

Writes our contributing editor Ricki Lewis:
In the Star Wars saga, George Lucas took great pains to keep Luke and Leia from kissing, knowing (when the audience didn't) that they were twins. Similarly, on the Young and the Restless, when newlyweds Billy and Mac discovered they shared a grandparent just seconds before they were to consummate their union, they backed away from each other in horror. Annulment followed.

gGenetics provides sound reasons for avoiding procreation with a blood relative. Consanguinity ("shared blood") can team up recessive genes inherited from shared ancestors, creating the curious situation of an otherwise extremely rare disorder striking more than one family member. Such families have led geneticists to many interesting genes - a search of the American Journal of Human Genetics for "consanguinity" in article titles yields nearly 4,000 hits. Within families, though, consanguinity can have tragic results. But for such personal behaviors as partner choice and having children, should outsiders intervene, even if their motives are to prevent suffering?

The "Ick" Factor
In a small, isolated town in northern Pakistan, a 10-year-old boy entertained crowds by stabbing knives through his arms and walking on hot coals - until one day at age 13 he jumped off a roof and died. At least six others in the community had the same strange pain insensitivity. Researchers studying the complexly connected families in the area discovered a mutation that blocks pain messages from entering nerve cells. DNA sequencing revealed that the errant gene had spread through shared ancestors.

A fictional victim of consanguinity is Calliope Stephanides, the hero/heroine of the Pulitzer-prizewinning "Middlesex", by Jeffrey Eugenides. The protagonist, raised as a girl, reached puberty and grew a penis - all because his paternal grandparents, isolated and frightened during wartime in a remote Greek village, united in their desperation. They were brother and sister.

The "ick factor" associated with consanguinity is perhaps why Patrick Stuebing and Susan Karolewski, the parents of four young children in Leipzig, Germany, recently made headlines. They, too, are brother and sister, and according to reports, two of their offspring have unspecified disorders. But Patrick was adopted, and didn't meet his biological family until age 23, when he and Susan fell in love. The government has placed three of the children in foster care and Patrick has already served one jail term, because incest is illegal. But sibling pairings are rare; more common are cousin couples. In the U.S. 24 U.S. states ban first cousin marriages. The birth defect risk for all types of consanguinity is about 8 percent, compared to 3 percent for all births.

Consanguinity to Conserve Resources
Genetics is only part of the inbreeding story. For Calliope's grandparents and for the German couple, love trumped DNA. In some times and places, consanguinity was actually encouraged, usually to keep resources within a family. Consider Egypt's Ptolemy dynasty. From 323 B. C. to Cleopatra's death in 30 B. C., the clan had one cousin-cousin pairing, four brother-sister unions, and an uncle-niece duo. Cleopatra herself wed her 10-year-old brother. Their pedigree (family tree) reflects this inbreeding. The term "pedigree" is from the French for "pie de grue", which means "crane's foot", because the typical chart widens with each generation, shaped like a bird's foot. The Egyptian pedigree resembles a ladder.

Marrying within the family to sequester resources persists. Today, 20 to 50 percent of marriages in some parts of the Middle East, Africa, and India are between cousins or uncles and nieces. In families unfortunate enough to keep their bad genes along with their wealth, results are heartbreaking. NPR recently ran a report, "Syrian Village Hobbled by Years of Inbreeding", about a community of 5,000 where 800 children have inherited a combination of blindness, mental retardation, and physical disabilities such as short limbs. The condition remains undiagnosed, but almost surely comes from more than 100 years of cousin-cousin marriages - encouraged to avoid paying a dowry. A teacher in the village is trying to attract outside attention to their plight, but he is outnumbered by those who do not wish to challenge "God's will".

Unknowing Consanguinity
Inbreeding undoubtedly occurs without people knowing it, especially in tight knit communities where few people leave or enter. This has happened with the Ashkenazi Jews, whose numbers plummeted so sharply during various periods of history that marriages of blood relatives were almost inevitable. Genocide has left a legacy of a dozen recessive disorders that are much more common among Jews than other population groups. But the Jewish people have done something about it. Thanks to genetic screening begun in the 1970s, the few cases of Tay-Sachs disease occurring in the U.S. today are notably not in Jewish people, in whom carrier-carrier couplings have been identified and steps taken to avoid the matching up of deleterious alleles. (The Law and Order: Special Victims Unit rerun on TV as I write this was wrong in portraying Tay-Sachs as a Jewish-only disease.)

The success of screening for Tay-Sachs disease carriers inspired a program that could serve as a model for other populations. The brainchild of an orthodox rabbi in Brooklyn who had lost four children to Tay-Sachs, Dor Yeshorim was founded in the early 1980s to test young people for the "Jewish genetic diseases". Results are stored in a confidential database, and when two people wish to marry, the information is unblinded. Couples who carry the same recessive disorder may alter their plans, either to marry or to have their own children. More than 100,000 people have been screened, and many families have avoided genetic disease.

So what should be done, if anything, to combat the health consequences of inbreeding? It might be a tough battle, since worldwide about 960 million couples are related, and know it. I'd vote for education - informing people of how and why marrying relatives sets the stage for disease - but not go so far as to disrespect long-held local customs and dictate who people can marry. Genetic medicine is largely about choice, and that should hold true for countering consanguinity.

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