Suzanne Leal, Ph.D.
Professor, Molecular and Human Genetics
SCBMB Executive Committee Member
Baylor College of Medicine
Ph.D., Epidemiology, Columbia University
Dr. Leal's is interested 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, she is also interested in methodological research.
The methodological aspect of her 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. Dr. Leal has 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 she 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 her group is the development of methods to analyze rare variants including rare copy number variants. This research has lead to the development of the Combined Multivariate and Collapsing (CMC) and the Kernel Based Adaptive Cluster (KBAC) methods to test for rare variant associations with Complex Traits. A current project involves the development of methods to map rare variants associated with quantitative traits using data from siblings as well as unrelated individuals with extreme quantitative traits. She is also investigating strategies to replicate findings from exome sequencing studies. With the development of next generation sequencing technologies (e.g. Roche 454, Ilumina HiSeq, ABI SOLiD), a wealth of data on rare variants from both entire exomes and whole genomes will become available, making these methodological tools increasingly important.
On the applied side, Dr. Leal has been involved in the study of a variety of phenotypes including: opiate metabolism, pain perception, platelet reactivity, bipolar disease, prostate & breast cancer and coronary diseases (i.e. LVOTO and aneurism & dissection) and non-syndromic hearing impairment. 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.
Dr. Leal is 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 (ACTG1, ESRRB, GRXCR1, HFG, and WFSI) 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.
Dr. Leal organizes and teaches at annual gene mapping courses at the Rockefeller University (New York, NY, USA), Max Delbrück Center (Berlin, Germany) and Helmholtz Institute (Munich, Germany). Recently I have taught statistical genetics courses at Beijing University (Beijing, Peoples Republic of China), European School of Genetic Medicine (Bologna, Italy), University of Helsinki (Helsinki, Finland) and University of Oslo (Oslo, Norway).
- Santos-Cortez RL, Lee K, Azeem Z, Antonellis PJ, Pollock LM, Khan S, Irfanullah, Andrade-Elizondo PB, Chiu I, Adams MD, Basit S, Smith JD, University of Washington Center for Mendelian Genomics, Nickerson DA, McDermott BM Jr, Ahmad W and Leal SM. Mutations in KARS, Encoding Lysyl-tRNA Synthetase, Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB89. Am J Hum Genet, [Epub ahead of print] (2013). PubMed
- Lee K, Chiu I, Santos-Cortez R, Basit S, Khan S, Azeem Z, Andrade P, Kim S, Ahmad W and Leal S. Novel OTOA mutations cause autosomal recessive non-syndromic hearing impairment in Pakistani families. Clin Genet, [Epub ahead of print] (2012). PubMed
- McDonald ML, MacMullen C, Liu DJ, Leal SM and Davis RL. Genetic association of cyclic AMP signaling genes with bipolar disorder. Transl Psychiatry, 2:e169 (2012). PubMed
- Liu DJ and Leal SM. Estimating genetic effects and quantifying missing heritability explained by identified rare-variant associations. Am J Hum Genet, 91(4):585-96 (2012). PubMed
- Li B, Wang G and Leal SM. SimRare: a program to generate and analyze sequence-based data for association studies of quantitative and qualitative traits. Bioinformatics, 28(20:2703-4 (2012). PubMed
- Liu DJ and Leal SM. SEQCHIP: a powerful method to integrate sequence and genotype data for the detection of rare variant associations. Bioinformatics, 28(13):1745-51 (2012). PubMed
- Liu DJ and Leal SM. A unified framework for detecting rare variant quantitative trait associations in pedigree and unrelated individuals via sequence data. Hum Hered, 73(2):105-22 (2012). PubMed
For more publications, see listing on PubMed.
Department: Molecular & Human Genetics
Address: Baylor College of Medicine
One Baylor Plaza
Houston, TX 77030
Additional Links: Leal Lab