Richard H. Finnell, Ph.D.
1980, University of Oregon Health Sciences Center-Portland
Texas A&M Institute of Biosciences and Technology
Center for Environmental and Genetic Medicine
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Richard H. Finnell, Ph.D. 1980, University of Oregon Health Sciences Center-Portland Texas A&M Institute of Biosciences and Technology |
Research Interests:
My laboratory is serving as the mutation analysis laboratory for the states of California and Texas in support of their participation in the National Birth Defects Prevention Study. These are two of the eight CDC recognized Centers of Excellence. As part of this research program, we are using multiple approaches to determine single nucleotide polymorphism (SNPs) in candidate genes for common, complex human birth defects, including: neural tube defects (spina bifida and anencephaly), craniofacial defects (cleft lip with or without cleft palate and their isolated forms), as well as conotruncal heart defects. Based on the hypothesis that individuals with genetically determined abnormalities in their folate receptors or folate transporter genes are less capable of binding both dietary and/or supplemental folic acid for transport to the placenta and harvest by the fetus during critical developmental periods, we are currently examining the genes coding for 5-methyletrahydrofolate receptor (FRa and FRd), reduced folate carrier (RFC1), methionine synthase (MTR) and methionine synthase reductase (MTPRR) and several other candidate genes in a high-throughput manner.
Based on the hypothesis that gene regulatory elements may also contribute to deficient gene products and consequently lead to abnormal embryonic development, we are currently looking for sequence variants in the promoter region and 5'-UTR of several candidate genes including: platelet derived growth factor alpha (PDGFa) receptor, RFC1, FRa (putative IRES element), VEGF, MTHFR (CpG island) in patients with selected birth defects. PDGFa receptor has been considered as candidate gene for human spina bifida based primarily upon mouse studies. We are currently screening the promoter haplotypes in a Hispanic population using a case-control approach. At the same time, gene transfection studies are being carried out to determine the transcriptional activity amongst the different haplotypes. For the FRa gene, we are actively cloning the putative Internal Ribosome Entry Site (RES) element from transcriptional variant 3, and determining the function of this element. For MTHFR gene, we are using bisulphate-sequencing method to determine the existence of CpG Island as well as its regulatory function.