Identification of genes is a prerequisite to understanding the biological basis of a disease. Statistical analyses are vital and necessary components of any gene-mapping effort. These methods include various linkage analysis, segregation analysis, candidate gene analysis, association mapping, admixture mapping, population genetics and meta-analysis.

The central focus of my research is to study the genetic epidemiology of complex diseases in which the inheritance does not follow clear-cut Mendelian fashion. These studies involve analyses of large numbers of phenotypically well-characterized families and case-control samples. The advent of new molecular genetic technologies makes the mapping and identification of susceptibility genes, and their interactions with other genes and environmental factors feasible. The disease in which we are mostly interested is systemic lupus erythematosus and non-syndromic cleft lip with or without cleft palate (NSCLP).

We have conducted several genome scans to identify chromosomal regions likely to harbor lupus susceptibility genes. Additionally, we are looking at candidate genes in the linked and other chromosomal regions for association with the disease. Currently, my lab is involved in the positional cloning and identification of major lupus susceptibility genes at 2q22-24, 5p15, 12q24, 16p12-q13, and Xq28 by combining data from linkage and allelic association. We are also performing mapping by admixture linkage disequilibrium (MALD), a powerful and cost-effective method to map the genes with low-penetrant risk. The key advantage of MALD is that a small number of ancestry informative markers are sufficient to map these lupus susceptibility loci. At present, we are applying MALD techniques to the study of African-American populations.

NSCLP is one of the most common craniofacial malformations. Both genetic and environmental factors are involved in the pathogenesis. Recently, based on a high-density genome scan, we have identified 13q33.1-p34 as a novel NSCLP susceptibility region. Fine mapping is underway to identify the actual susceptibility gene.