Highlights from the November 2010 Issue of DNA and Cell Biology

D NA and Cell Biology often features studies of single nucleotide polymorphisms, analyzed separately or as haplotypes, with links to disease. This month's issue features two articles analyzing a potential correlation between single nucleotide polymorphisms and development of cleft lip with or without cleft palate. Jia and colleagues' study, “Association Between Polymorphisms at Small Ubiquitin-Like Modifier 1 and Nonsyndromic Orofacial Clefts in Western China,” along with “Association Analysis of the Poliovirus Receptor Related-2 Gene in Patients with Nonsyndromic Cleft Lip with or Without Cleft Palate” by Chengle et al., explore the roles of single nucleotide polymorphisms in two genes possibly contributing to the development of this birth defect. These articles join three similar analyses previously published this year and one in press that examined potential correlations among single nucleotide polymorphisms and cleft lip. This abundance of articles raises the question of why we should focus on potential genetic factors contributing to this condition.

The frequency and significant consequences of this birth defect may partially explain the interest in cleft lip research. This birth defect occurs throughout the world in approximately one in every 700 births. However, there is extensive variation in its prevalence among ethnic groups. Cleft lip is more common in Northern Europeans, Asians, Native Americans, and Aboriginal Australians, and very rare in those of African descent (reviewed in Vieira, 2008). Cleft lip, which may also include cleft palate, is a birth defect of the upper lip and the roof of the mouth resulting from a failure of the tissue to join before birth. Lip and palate formation requires several processes, including cell proliferation, differentiation, adhesion, and apoptosis (Vieira, 2008). Thus this developmental program likely requires the proper expression of multiple genes and their functional products. Disruption of this developmental cascade may result in cleft lip with or without cleft palate and significant consequences for the child. This condition can cause feeding difficulties, dental problems, as well as hearing or speech delays for the child and is often corrected via surgery at around one year of age. However, children born with cleft lip have a shorter life span and increased incidence rates of cancer and psychiatric disorders (Vieira, 2008). Thus there is a need to understand the triggers of this condition and any interactions with the causes of other chronic illnesses.

The proposed causes of cleft lip provide additional rationale for single nucleotide polymorphism studies. Cleft lip is thought to be caused by a combination of genetic factors, such as mutations in IRF6 and MSXI and an estimated 3 to 14 additional genes, and environmental influences, including maternal cigarette smoking or lack of dietary folate, which may interact with each other (Vieira, 2008). The studies published in DNA and Cell Biology are working to identify the other genes that may contribute to development of cleft lip.