Section of Perinatal Medicine

• Jeffrey R. Gruen, MD, Associate Professor
  Special Interest: Genetics of Complex Disorders

Non-Faculty members (technical, clerical)

• Marcel Nabors, Adminstrative Assistant

Fellows and other trainees

• Haiying Meng, MD, Post-Doctoral Fellow

Current Grant Support

Name	Title	Funding Agency	Dates
JR Gruen	Characterization of the thymus specific serine protease (TSSP) gene	Charles H. Hood Foundation	1/1/98 - 5/30/03

Publications for 2001 and 2002:

Original reports:
1. Gruen JR and Weissman SM. Human MHC class III and IV genes and disease associations. Frontiers in Bioscience, 6:D960-D972, 2001.

2. Hisama FM, Gruen JR, Choi J, Huseinovic M, Grigorenko EL, Pauls D, Mattson RH, Gelernter J, Wood FB, Goei VL. Human GABAB receptor 1 gene: eight novel sequence variants. Human Mutation, 17(4):349-350, 2001.

3. Ahn J, Won T-W, Zia A, Reutter H, Kaplan DE, Sparks R, Gruen JR. Peaks of linkage are localized by a bac/pac contig of the 6p reading disability locus, Genomics, 78(1/2):19-29, 2001.

4. Barr CL, Feng Y, Wigg K, Roberts W, Malone M, Schachar R, Tannock R, Gruen JR, Goei V, Kennedy JL. Identification of polymorphisms in the GABAB receptor gene located on chromosome 6p and linkage study of attention-deficit hyperactivity disorder. Gene Function and Disease, 1:194-201, 2001.

5. Lie BA, Akselsen HE, Bowlus CL, Gruen JR, Thorsby E, Undlien, DE, Polymorphisms in the gene encoding thymus-specific serine protease in the extended HLA complex. A potential candidate gene for HLA associated diseases, Genes and Immunity, 3(5):306-312, 2002.

6. Ahn J, Won T-W, Kaplan DE, Londin ER, Kuzmic P, Gelernter J, Gruen JR. A detailed physical map of the 6p reading disability locus including new markers and confirmation of recombination suppression, Human Genetics, 111:339-349, 2002.

7. Kaplan DE, Gayan J, Ahn J, Won T-W, Pauls D, Olson R, DeFries J, Wood F, Pennington B, Page G, Smith SD, Gruen JR. Linkage and association studies of reading disability on 6p21.3-22, The American Journal of Human Genetics, 70(5):1287-1298, 2002.

8. Cheunsuk S, Sparks R, Noveroske JK, Hsu T, Justice MJ, Gershwin ME, Gruen JR and Bowlus CL. Expression, genomic structure and mapping of the thymus specific protease Prss16: a candidate gene for insulin dependent diabetes mellitus susceptibility. Journal of Autoimmunity, 18:311-316, 2002.

Reviews and Chapters:
1. Chu TW, Bowlus CL, Gruen JR. Iron metabolism and related disorders. In: Rimoin DL, Connor JM, Pyeritz RE, and Emery AEH, ed. Emery and Rimoin’s principles and practice of medical genetics. 4th edition. Churchill Livingston Publishers, Edinburgh, United Kingdom, Volume II, 2002, 2638-2665.

2. Sparks R and Gruen JR. Molecular diagnostics in childhood disorders. In: Rudolph CD, Rudolph AM, Hostetter, M, Lister, G, Siegel, N, ed. Rudolph’s Pediatrics. 21st edition. McGraw-Hill Medical Publishing Company, Philadelphia, 2002, 573-578.

Research Interests and Activity
Our primary research interest is the identification of susceptibility genes for reading disability, commonly known as “dyslexia.” Dyslexia is present in 10 to 20% of all school children and accounts for more than 80% of learning disabilities. While acquisition of skilled reading is to a great extent influenced by environmental factors such as exposure to print media, story reading, and early childhood education, our group and others have shown that 50% or more of the deficits in dyslexic children can be attributed to risk factors inherited from their parents. These risk factors are variant alleles of a small number of genes at loci yet to be precisely identified on human chromosomes 18, 15, 6, 3, 2, and 1. To localize the strongest acting of these genes on chromosome 6, our lab is currently doing genetic testing of dyslexic subjects and correlating alleles and haplotypes (allele combinations from several markers) with reading performance. Through the Yale Center for the Study of Learning and Attention Disorders, we are also collecting functional magnetic resonance imaging (fMRI) data on dyslexic children. fMRI consistently shows that the normal neural circuitry activated in reading is disrupted in dyslexics. By conditioning our genetic studies on the new fMRI data, we hope to be able to identify those genes that govern the normal development of these neural circuits. Ultimately, identification of susceptibility genes and alleles will change the way we think about dyslexia, the way we diagnose it, and the way we treat it. Currently, a large number of dyslexic readers are missed until they reach the high school years. By then, poor school performance often heralds poor self-esteem and encourages a high dropout rate. Early genetic screening will guide children into remedial programs in the pre-reading years, which can make a marked difference in academic achievement and self-esteem. Sub-classifying dyslexics by molecular diagnosis may improve how we match students with specific interventions and improve outcomes. Learning more about the molecules in the brain that govern fluent reading may even, some day, suggest useful pharmacotherapies.