Professor, Department of Molecular and Human Genetics

B.S., Fordham University, New York, 1981
M.S., Columbia University, New York, 1989
Ph.D., Columbia University, New York, 1994
Postdoc, University of Tübingen, Tübingen, Germany, 1996

RESEARCH INTERESTS:

My interest in statistical genetics/genetic epidemiology lies in the mapping of complex and Mendelian traits and understanding the interactions between genes and between genes and the environment. In addition to applied work of localizing disease loci through statistical genetic methods, I am interested in methodological research.

The methodological aspect of my work has included recently the development of the SimPed program which can stimulate haplotype and genotype data for thousands of marker loci for large complex pedigree structures. I have also examined the ability to detect genotyping error and pseudo-SNPs via deviations from Hardy-Weinberg equilibrium (HWE) as well as studied the effect of ascertainment on deviation from HWE. Recently I examined the effect of intermarker linkage disequilibrium in consanguineous pedigrees and demonstrated that missing genotype data from any pedigree member can increase false-positive evidence of linkage. Currently, a major interest of my group is the development of methods to analyze rare variants. With the development of sequencing technology (e.g. 454 and Solexa) which will provide a wealth of data on rare variants these methodological tools will become increasingly important.

On the applied side, I have been involved in the study of a variety of phenotypes including: opiate metabolism, pain perception, platelet aggregation, bipolar disease, prostate cancer, breast cancer and coronary diseases (i.e. LVOTO and aneurism and dissection) and non-syndromic hearing loss. A variety of statistical genetic methods are implemented to analyze the data including parametric and non-parametric linkage analyses and statistical methods for association studies.

I am the Principal Investigator of a study on non-syndromic hearing impairment (NSHI) which is supported by the NIH-NIDCD. The study is recruiting individuals with a family history of NSHI from Pakistan, Switzerland, Jordan, Turkey, and the United States. The major goals of the study are to localize and identify NSHI genes. Additional goals of the study include understanding genotyping/phenotype relationships and prevalence of specific loci/mutations. The study has lead to the identification of a number of genes for NSHI (WFSI, ESRRB and ACTG1) and novel loci including DFNA23, DFNA24, DFNB35, DFNB38, DFNB39, DFNB44, DFNB45, DFNB46, DFNB47, DFNB55, DFNB62, DFNB65, DFNB68 and DNFB71. The spectrum of variants and the population-specific prevalence rates have also been studied for NSHI genes GJB2, TMC1, TMIE and TRIC.

I teach courses in statistical genetics/genetic epidemiology internationally. I also organize advanced and basic gene mapping courses that are held annually at The Rockefeller University, New York, GSF Munich, Germany, and the Max Delbrück Center, Berlin, Germany. These courses cover the theoretical aspects of statistical analysis with hands-on experience of analyzing data using computer programs that implement the various algorithms which are discussed at the course.

SELECTED PUBLICATIONS:

1. Li B, Leal SM (2008). Deviation from Hardy-Weinberg equilibrium in parental and unaffected sibling genotype data. Hum. Hered., in press.

2. Li B, Leal SM (2008). Novel Methods for Detecting Associations with Rare Variants for Common Diseases: Application to Analysis of Sequence Data. Am. J. Hum. Genet. 83: 311-321.

3. Collin RW, Kalay E, Tariq M, Peters T, van der Zwaag B, Venselaar H, Oostrik J, Lee K, Ahmed ZM, Caylan R, Li Y, Spierenburg HA, Eyupoglu E, Heister A, Riazuddin S, Bahat E, Ansar M, Arslan S, Wollnik B, Brunner HG, Cremers CW, Karaguzel A, Ahmad W, Cremers FP, Vriend G, Friedman TB, Riazuddin S, Leal SM, Kremer H (2008). Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35. Am. J. Hum. Genet. 82: 125-138.

4. Li B, Leal SM (2008). Ignoring intermarker linkage disequilibrium induces false-positive evidence of linkage for consanguineous pedigrees when genotype data is missing for any pedigree member. Hum. Hered. 65: 199-208.

5. Sabeti PC, et al. (2007). Genome-wide detection and characterization of positive selection in human populations. Nature 449: 913-918.

6. International HapMap Consortium (2007). A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851-861.

7. Leal SM (2005). Detecting genotyping errors and pseudo-SNPs via deviations from Hardy Weinberg equilibrium. Genet. Epidemiol. 29: 204-214.