For the first time scientists have discovered a specific gene variant that has been linked to cleft lip alone, rather than cleft lip and palate. It provides an insight into a previously unknown genetic mechanism.
What Causes Cleft Lip?
The study of human genetics is opening up windows on a previously hidden biological world. Geneticists are trying to get to grips with the underlying basic genetics of many different conditions that plague humans. One of those is cleft lip (a split in the upper lip) and previously researchers had indentified a gene known as IRF6 as playing a role in about 12% of cleft lip and palate cases. People with cleft lips experience difficulty swallowing, chewing and speaking.
This time round an international team of scientists went back to IRF6 to take a closer look to help them understand more about what causes cleft lip. The lead author was Fedik Rahimov from the University of Iowa and the research was published in the October 5th edition of the journal 'Nature Genetics.'
IRF6
Their research was a mixture of computational and biological methods, human genetics and nonhuman genetics. They isolated a regulatory region on a nonhuman section of IRF6. Regulatory regions are those parts of the DNA structure that affect the protein coding regions of a gene.
They found a single nucleotide variant, so the next step was to see if this was also present in human IRF6. They found it - inside a regulatory element that controls IRF6 expression.
The next stage was to see if this variant was common in people with cleft lip and palate. The researchers studied the DNA of 3,000 families and found that those with cleft lip were far more likely to have the gene variant.
Basic Genetics of IRF6
The basic genetic mechanism that the researchers uncovered was that the variant disrupts the ability of AP2 protein to bind to it, and this disrupts the expression of the IRF6 gene.
Having now discovered this, it's hoped that the knowledge will help with the diagnosis, treatment and possibly prevention of cleft lip, which is believed to affect 5 million people around the world. Whilst there are surgical procedures to correct the abnormality, it is not a complete solution for everybody.
The research will also have important implications for those parents who have children with cleft lip and undergo genetic counselling.