In the 1960s, Habiba Chaabouni was one of a handful of women enrolled in medical school in Tunisia. There, she often met families with two or three sick children. "There was a lot of chronic disease," she recalls, and she wanted to find out why.
In some ways, Tunisia is a geneticist's paradise. The native population primarily derives from the Arab-Berber ethnic group, which favors frequent consanguineous marriages (still around one-third of unions), resulting in a host of genetic diseases including thalassemia, mental retardation, and birth defects. The country borders Algeria, Libya, and the Mediterranean, and juts out toward Sicily, so it has been infiltrated by a succession of diverse nations: the Phoenicians, Romans, Byzantines, and the French. All of this paints an interesting genetic picture.
It wasn't an easy one to analyze. When Chaabouni graduated from medical school, there was no infrastructure or facilities in Tunisia to study genetic diseases. In those early days, she collaborated with European scientists, gathering samples from Tunisians, and then accompanying the samples on a flight to France, where she processed the findings. "In the beginning I worked for myself, by myself." Over time, she began interacting with government representatives, urging them to build up resources within her native land. She met with policymakers and the dean of the medical school, wrote to newspapers and colleagues abroad, and appeared on television to make her case. The issue, she says, was a lack of both resources and interest in genetics. But she was persistent: "I used all of the tools," she says, laughing.
Chaabouni would become the first Tunisian scientist to study genetic disease. To date, she has coauthored more than 40 studies of the genetic underpinnings of the diseases that caught her attention as a young doctor. In the first study of consanguinity in Tunisia, published in 1987 in the journal La Tunisie Médicale, she took samples from healthy people in the north of the country and asked them about their family history of intermarriage. Not surprisingly, she found that the level of consanguinity was higher in rural areas than in cities, and people often did not appreciate the problem.
"People in that time, and even now, are not convinced of the importance of consanguinity," she says. "It's something that's still prevalent in Tunisia. Even among young people, they marry their cousin."
Chaabouni is no longer working alone: approximately 100 Tunisian scientists and other professionals now work in genetics research. "Today, I have a team," says Chaabouni, who conducts her research at the Laboratory of Human Genetics in Tunis.
In 2004, Chaabouni led a group of researchers who performed the first screening in the Arab population for mutations of the 21-hydroxylase gene (J Clin Endocrinol Metab, 89:368-74, 2004). Defects in this gene can cause congenital adrenal hyperplasia, a hormone disorder that triggers male characteristics such as deep voices and facial hair in girls, and early puberty in boys as young as 2 years old.
Chaabouni also collaborated with NIH researchers to study 19 consanguineous Tunisian families with Bardet-Biedl syndrome, which comes with vision problems, obesity, and polydactyly (extra fingers and/or toes). The researchers found that none of the families carried a rare inheritance pattern that previous research has identified in Bardet-Biedl, illustrating the disease's heterogeneity (Invest Ophthalmol Vis Sci, 47:3487-95, 2006).
Last year, Chaabouni led a team that found that the frequency and distribution of the gene behind familial Mediterranean fever in Tunisia is different from that seen in other Arab populations, and resembles patterns among Turkish populations (Semin Arthritis Rheum, 36:397-401, 2007). This makes sense, says Chaabouni; hundreds of years ago, Tunisia was part of the Ottoman Empire, so many Tunisian families originated from Turkey.
Given the ongoing high rate of consanguinity, Chaabouni still spends half her time counseling Tunisians with familial diseases. Patients react differently to the news that their decision to intermarry may have caused their children to develop genetic disease, she says. Some people don't accept the fact that they have genes and that these genes caused the illness, but some people, like her, understand and want to know "more and more."